Secreted human proteins

ABSTRACT

Secreted proteins can be identified using a method which exploits the ability of microsomes to modify proteins post-translationally. Nineteen human secreted proteins and full-length cDNA sequences encoding the proteins have been identified using this method. The proteins and cDNA sequences can be used, inter alia, for targeting other proteins to the membrane or extracellular milieu.

[0001] This application claims the benefit of copending provisional application Serial No. 60/032,757, filed Dec. 11, 1996, which is incorporated herein by reference.

TECHNICAL AREA OF THE INVENTION

[0002] The invention relates to the area of proteins. More particularly, the invention relates to human secreted proteins.

BACKGROUND OF THE INVENTION

[0003] Secreted proteins include such important proteins as growth factors, cytokines and their receptors, extracellular matrix proteins, and proteases. Nucleotide sequences encoding these proteins can be used to detect disease states in which such proteins are implicated and to develop therapeutics for such diseases. Thus, there is a need in the art for methods of identifying secreted proteins and the nucleotide sequences which encode them.

SUMMARY OF THE INVENTION

[0004] It is an object of the invention to provide an isolated and purified human protein.

[0005] It is yet another object of the invention to provide a fusion protein.

[0006] It is still another object of the invention to provide a preparation of antibodies.

[0007] It is even another object of the invention to provide an isolated and purified subgenomic polynucleotide.

[0008] It is yet another object of the invention to provide an isolated gene.

[0009] It is a further object of the invention to provide a DNA construct for expressing all or a portion of a human protein.

[0010] It is still another object of the invention to provide a host cell comprising a DNA construct.

[0011] It is another object of the invention to provide a homologously recombinant cell.

[0012] It is even another object of the invention to provide a method of producing a human protein.

[0013] It is another object of the invention to provide a method of identifying a secreted polypeptide which is modified by rough microsomes.

[0014] These and other objects of the invention are provided by one or more of the embodiments described below.

[0015] One embodiment of the invention provides an isolated and purified human protein. The isolated and purified human protein has an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38.

[0016] Another embodiment of the invention provides an isolated and purified human protein having an amino acid sequence which is at least 85% identical to an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38.

[0017] Still another embodiment of the invention provides a polypeptide comprising at least 6 contiguous amino acids of an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38.

[0018] Even another embodiment of the invention provides a fusion protein. The fusion protein comprises a first protein segment and a second protein segment fused together by means of a peptide bond. The first protein segment consists of at least 6 contiguous amino acids selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38.

[0019] Yet another embodiment of the invention provides a preparation of antibodies. The antibodies specifically bind to a human protein having an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38.

[0020] Even another embodiment of the invention provides an isolated and purified subgenomic polynucleotide. The isolated and purified subgenomic polynucleotide has a nucleotide sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0021] Yet another embodiment of the invention provides an isolated and purified subgenomic polynucleotide consisting of at least 10 contiguous nucleotides selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0022] Still another embodiment of the invention provides an isolated gene. The isolated gene corresponds to a cDNA sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0023] Another embodiment of the invention provides a DNA construct for expressing all or a portion of a human protein. The DNA construct comprises a promoter and a polynucleotide segment. The polynucleotide segment encodes at least 6 contiguous amino acids of a human protein having an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38. The polynucleotide segment is located downstream from the promoter. Transcription of the polynucleotide segment initiates at the promoter.

[0024] Even another embodiment of the invention provides a host cell comprising a DNA construct. The DNA construct comprises a promoter and a polynucleotide segment. The polynucleotide segment encodes at least 6 contiguous amino acids of a human protein having an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38. The polynucleotide segment is located downstream from the promoter. Transcription of the polynucleotide segment initiates at the promoter.

[0025] Still another embodiment of the invention provides a homologously recombinant cell having incorporated therein a new transcription initiation unit. The transcription initiation unit comprises in 5′ to 3′ order an exogenous regulatory sequence, an exogenous exon, and a splice donor site. The transcription initiation unit is located upstream to a coding sequence of a gene. The gene comprises a nucleotide sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19. The exogenous regulatory sequence controls transcription of the coding sequence of the gene.

[0026] Yet another embodiment of the invention provides a method of producing a human protein. A culture of a cell is grown. The cell comprises a DNA construct. The DNA construct comprises a promoter and a polynucleotide segment. The polynucleotide segment encodes at least 6 contiguous amino acids of a human protein having an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38. The polynucleotide segment is located downstream from the promoter. Transcription of the polynucleotide segment initiates at the promoter. The protein is purified from the culture.

[0027] Even another embodiment of the invention provides a method of producing a human protein. A culture of a cell is grown. The cell comprises a new transcription initiation unit. The transcription initiation unit comprises in 5′ to 3′ order an exogenous regulatory sequence, an exogenous exon, and a splice donor site. The transcription initiation unit is located upstream to a coding sequence of a gene. The gene comprises a nucleotide sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19. The exogenous regulatory sequence controls transcription of the coding sequence of the gene. The protein is purified from the culture.

[0028] Another embodiment of the invention provides a method of identifying a secreted polypeptide which is modified by rough microsomes. A population of cDNA molecules is transcribed in vitro whereby a population of cRNA molecules is formed. A first portion of the population of cRNA molecules is translated in vitro in the absence of rough microsomes whereby a first population of polypeptides is formed. A second portion of the population of cRNA molecules is translated in vitro in the presence of rough microsomes whereby a second population of polypeptides is formed. The first population of polypeptides is compared with the second population of polypeptides. Polypeptide members of the second population which have been modified by the rough microsomes are detected.

[0029] The present invention thus provides the art with a method for identifying secreted proteins or polypeptides, the amino acid sequences of nineteen novel human secreted proteins, and the nucleotide sequences which encode these proteins. The invention can be used to, inter alia, to produce secreted proteins for therapeutic and diagnostic purposes.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0030] The inventors have discovered a method for identifying secreted proteins or polypeptides. Secreted proteins or polypeptides include soluble proteins which can be transported across a membrane, such as a cell membrane, nuclear membrane, or membrane of the endoplasmic reticulum, as well as proteins which can be partially secreted from a cell, such as membrane-bound receptors.

[0031] Secreted proteins can contain a signal (or secretion leader) sequence, located at the N-terminus and including at least several hydrophobic amino acids, such as phenylalanine, methionine, leucine, valine, or tryptophan. Non-hydrophobic amino acids can also be included in the signal sequence. Signal sequences are described in von Heijne, J. Mol. Biol. 184:99-105 (1985) and Kaiser and Botstein, Mol. Cell. Biol. 6:2382-2391 (1986). Secreted proteins can also be glycosylated by post-translational modification. The presence of a signal sequence or the presence of glycosylation or both indicate that a particular protein is a secreted protein.

[0032] In order to identify secreted proteins or polypeptides, the method of the invention exploits properties of microsomes, which are the closed vesicles that result from fragmentation of endoplasmic reticulum. Microsomes can be rough or smooth, depending on whether the endoplasmic reticulum from which they were derived is studded with ribosomes, Microsomes, particularly rough microsomes, have the ability to perform post-translational modifications, such as glycosylation and cleavage of signal sequences from proteins or polypeptides.

[0033] To identify secreted proteins, a population of complementary DNA (cDNA) molecules is transcribed in vitro to synthesize a population of complementary RNA (cRNA) molecules. The cDNA molecules can be synthesized by reverse transcription of mRNA molecules isolated from a particular cell or tissue type or organism using, for example, a commercially available reverse transcriptase enzyme. Alternatively, the reverse transcription reaction to form cDNA molecules can be conducted on total RNA, without a preliminary purification of mRNA.

[0034] Any organism, such as a bacterium, plant, invertebrate, or vertebrate organism, can be used as a source of RNA. Particularly preferred sources of RNA are mammals, most preferably humans. Tissues, such as liver, brain, kidney, spleen, pancreas, or muscle, can be used as a source of RNA. Individual cell types, either primary cells or members of established cell lines, such as HeLa, CHO, PC12, P19, BHK, COS, or HepG2, are suitable sources of RNA. Tissues or primary cells isolated from organisms at a particular stage in development can be used as RNA sources. Stem cells, such as hematopoietic, neuronal, and embryonic stem cells, can also be used as a source of RNA.

[0035] Total RNA or mRNA can be isolated using methods known in the art. Such methods are described, inter alia, in Sambrook et al., MOLECULAR CLONING, A LABORATORY MANUAL (2d ed., Cold Spring Harbor Press, N.Y., 1989), and Ausubel et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY (Greene Publishing Associates and John Wiley & Sons, N.Y., 1994). Techniques for RNA isolation can be tailored for a particular organism or cell type, as is known in the art.

[0036] Complementary DNA can optionally be obtained from a cDNA library. The cDNA library can be derived from the genome of any organism of interest, particularly a mammal or a human. Tissue- or cell type-specific cDNA libraries can also be used as a source of cDNA.

[0037] Transcription of cDNA molecules in vitro to form cRNA molecules can be carried out using any methods known in the art. These methods include, for example, placing cDNA into a cloning vector containing a promoter, such as an SP6, T7, or T3 polymerase promoter, and transcribing the cDNA using the appropriate polymerase. A variety of commercial kits are available for this purpose.

[0038] A first portion of the population of cRNA molecules can be translated in vitro, in the absence of rough microsomes, to form a first population of polypeptides which have not been post-translationally modified. A second portion of the population of cRNA molecules can be translated in vitro in the presence of rough microsomes. Under the conditions of the in vitro translation reaction, rough microsomes can cleave signal sequences from those polypeptides which comprise such sequences. Under the same conditions, rough microsomes can also glycosylate those polypeptides which contain glycosylation sites.

[0039] Methods of in vitro translation are those which are known in the art, such as translation in a reticulocyte lysate system, particularly a rabbit reticulocyte lysate. Reticulocyte lysate systems can be assembled in the laboratory or purchased commercially in kit form.

[0040] Microsomes can be prepared by disruption of tissues or cells by homogenization, as is known in the art. If desired, rough and smooth microsomes can be separated using well-known techniques, such as sucrose density gradient sedimentation. Microsomes are also available commercially, for example, such as the canine pancreatic microsomes available from Promega Corp., Madison, Wis.

[0041] The first population of polypeptides can then be compared with the second population of polypeptides. This comparison can be by means of, for example, one- or two-dimensional polyacrylamide gel electrophoresis, as is known in the art. Polypeptides separated in the gels can be detected by any means known in the art, such as staining with copper, silver, Coomassie Brilliant Blue, amido black, fast green FCF, Ponceau S, or a chromophoric label. Separated proteins can also be visualized using radioactive, chemiluminescent, fluorescent, or enzymatic tags incorporated into the proteins before separation.

[0042] The gels can be dried or the proteins can be transferred to membranes, such as polyvinylidene difluoride membranes. Either the gels or membranes themselves or photographs of the gels or membranes can be compared by eye. Alternatively, the gels or membranes can be scanned, for example, with a densitometer and analyzed with the aid of a computer.

[0043] Polypeptide members of the second population of polypeptides, which have been modified by the rough microsomes, can be detected by any means available in the art. For example, a shift in the position of a polypeptide band can be observed, indicating an increase in molecular weight of a member of the second population compared with the corresponding polypeptide member of the first population. Such an increase in molecular weight indicates that the polypeptide member of the second population was glycosylated by the rough microsomes.

[0044] A shift in the position of a polypeptide band indicating a decrease in molecular weight of a member of the second population compared with the corresponding polypeptide member of the first population can also be observed. This decrease in molecular weight indicates that the polypeptide member of the second population contained a signal sequence which was cleaved by the rough microsomes.

[0045] Polypeptides which are modified by the rough microsomes are identified as secreted polypeptides. Optionally, quantities of cDNA molecules which encode secreted polypeptides can be obtained. Molecules of cDNA which encode polypeptides which are post-translationally modified by the rough microsomes can be placed into suitable vectors using standard recombinant DNA techniques and used to transform host cells. Many vectors are available for this purpose, such as retroviral or adenoviral vectors and bacteriophage, as described below.

[0046] Vectors comprising cDNA which encode secreted polypeptides can be introduced into host cells using techniques available in the art. These techniques include, but are not limited to, transferrin-polycation-mediated DNA transfer, transfection with naked or encapsulated nucleic acids, liposome-mediated cellular fusion, intracellular transportation of DNA-coated latex beads, protoplast fusion, viral infection, electroporation, and calcium phosphate-mediated transfection.

[0047] The host cells can be any host cells which are capable of propagating cDNA molecules. A variety of host cells, for example immortalized cell lines such as HeLa, CHO, or HEK, are available for this purpose.

[0048] Transformed host cells can be diluted serially and cultured to form individual colonies. Methods of culturing host cells and the media suitable for each host cell type are well known in the art. Preferably, each colony originates from a single transformed host cell. Separate preparations of cDNA from each colony can be prepared, as described above, and transcribed in vitro to form cRNA. The cRNA can be transcribed to form secreted polypeptides, which can be purified as is known in the art. If the preparation of secreted polypeptides from a colony contains more than one species of polypeptide, the steps described above can be repeated until a colony is obtained which contains cDNA encoding only a single species of polypeptide.

[0049] Complementary DNA molecules which encode secreted proteins can be sequenced using standard nucleotide sequencing techniques. The sequence of each cDNA molecule can be compared with known sequences in a database to determine whether the clone encodes a known or a novel secreted protein.

[0050] The inventors have used the method of the invention to identify nineteen novel human secreted proteins. Amino acid sequences for these nineteen human secreted proteins are disclosed in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38. Nucleotide sequences which encode the proteins are disclosed in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19, respectively.

[0051] Clones containing the cDNAs of the secreted proteins were deposited on Dec. 11, 1997, with the ATCC. Individual bacterial cells (E. coli) in this composite deposit contain one or more of the polynucleotides encoding the secreted proteins of the invention and can be retrieved using an oligonucleotide probe designed from the sequence for that particular polynucleotide, as provided herein. Each polynucleotide can be removed from the vector by performing an EcoRI/NotI digestion (5′ site, EcoRI; 3′ site, NotI). The deposit submitted to the ATCC has been designated SECP120997. The nucleotide sequences of these deposits and the amino acid sequences they encode are controlling in the event of a discrepancy between the amino acid and nucleotide sequences disclosed herein and those contained in the deposits.

[0052] A purified and isolated subgenomic polynucleotide of the present invention comprises at least 10, 12, 15, 18, 20, 25, 30, 35, 40, 45, or 50 contiguous nucleotides selected from the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19. The isolated and purified subgenomic polynucleotides can comprise an entire nucleotide sequence selected from the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0053] Subgenomic polynucleotides contain less than a whole chromosome and are preferably intron-free. Polynucleotides of the invention can be isolated and purified free from other nucleotide sequences by standard nucleic acid purification techniques, using restriction enzymes and probes to isolate fragments comprising the coding sequences.

[0054] Isolated genes corresponding to the cDNA sequences disclosed herein are also provided. Known methods can be used to isolate the corresponding genes using the provided cDNA sequences. These methods include preparation of probes or primers from the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 for use in identifying or amplifying the genes from human genomic libraries or other sources of human genomic DNA.

[0055] The coding sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 can be made using reverse transcriptase with human mRNA as a template. Amplification by PCR can also be used to obtain the polynucleotides, using either genomic DNA or cDNA as a template. Polynucleotide molecules of the invention can also be made using the techniques of synthetic chemistry given the sequences disclosed herein. The degeneracy of the genetic code permits alternate nucleotide sequences which will encode the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38 to be synthesized. All such nucleotide sequences are within the scope of the present invention.

[0056] Polynucleotide molecules of the invention can be propagated in vectors and cell lines as is known in the art. Polynucleotide molecules can be on linear or circular molecules. They can be on autonomously replicating molecules or on molecules without replication sequences. For propagation, polynucleotides of the invention can be introduced into suitable host cells using any techniques available in the art, as described above.

[0057] Subgenomic polynucleotides of the invention can be used to propagate additional copies of the polynucleotides or to express protein, polypeptides, or fusion proteins. The subgenomic polynucleotides disclosed herein can also be used, for example, as biomarkers for tissues or chromosomes, as molecular weight markers for DNA gels, to elicit immune responses, such as the formation of antibodies against single- or double-stranded DNA, and in DNA-ligand interaction assays, to detect proteins or other molecules which interact with the nucleotide sequences.

[0058] Disease states may be associated with alterations in the expression of genes which encode proteins of the invention. Polynucleotide sequences disclosed herein can also be used to determine the involvement of any of these sequences in disease states. For example, a gene in a diseased cell can be sequenced and compared with a wild-type coding sequence of the invention. Alternatively, nucleotide probes can be constructed and used to detect normal or altered (mutant) forms of mRNA in a diseased cell. Subgenomic polynucleotides of the invention can also be used to design diagnostic tests and therapeutic compositions for diseases which may be associated with altered expression of these genes.

[0059] The present invention provides both full-length and mature forms of the disclosed proteins. Full-length forms of the proteins have the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38. The full-length forms of a protein can be processed enzymatically to remove a signal sequence, resulting in a mature form of the protein. Signal sequences can be identified by examination of the amino acid sequences disclosed herein and comparison with amino acid sequences of known signal sequences (see, e.g., von Heijne, 1985; Kaiser & Botstein, 1986). Similarly, transmembrane domains can be identified by examination of the amino acid sequences disclosed herein. A transmembrane domain typically contains a long stretch of 15-30 hydrophobic amino acids.

[0060] Other domains with predicted functions can also be identified. For example, the protein having the amino acid sequence shown in SEQ ID NO: 23 comprises a Kunitz type serine protease inhibitor domain spanning amino acids 68 to 122 of SEQ ID NO: 23. The protein having the amino acid sequence shown in SEQ ID NO: 20 contains a zinc-finger motif.

[0061] Allelic variants of the disclosed subgenomic polynucleotides can occur and encode proteins which are identical, homologous, or substantially related to amino acid sequences disclosed herein (see below).

[0062] Allelic variants of subgenomic polynucleotides of the invention can be identified by hybridization of putative allelic variants with nucleotide sequences disclosed herein under stringent conditions. For example, by using the following wash conditions—2×SCC, 0.1% SDS, room temperature twice, 30 minutes each; then 2×SCC, 0.1% SDS, 50° C. once, 30 minutes; then 2×SCC, room temperature twice, 10 minutes each—allelic variants can be identified which contain at most about 25-30% basepair mismatches. More preferably, allelic variants contain 15-25% basepair mismatches, even more preferably 5-15% basepair mismatches.

[0063] Protein variants of secreted proteins of the invention are also included. Amino acids which are not involved in regions which determine biological activity can be deleted or modified without affecting biological function. Preferably, protein variants of the invention have amino acid sequences which are at least 85%, 90%, or 95% identical to the amino acid sequences disclosed herein and have similar biological properties (see below). More preferably, the molecules are 98% identical. Modifications of interest in the protein sequences can include the alteration, substitution, replacement, insertion or deletion of a selected amino acid residue. Proteins or derivatives can be either glycosylated or unglycosylated. Techniques for making such modifications are well known to those skilled in the art (see, e.g., U.S. Pat. No. 4,518,584). Alternatively, variants of proteins disclosed herein can be constructed using techniques of synthetic chemistry or using recombinant DNA methods.

[0064] Preferably, amino acid changes in variants or derivatives of proteins of the invention are conservative amino acid changes, i.e., substitutions of similarly charged or uncharged amino acids. A conservative amino acid change involves substitution of one amino acid for another amino acid of a family of amino acids which are structurally related in their side chains. Naturally occurring amino acids are generally divided into four families: acidic (aspartate, glutamate), basic (lysine, arginine, histidine), non-polar (alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), and uncharged polar (glycine, asparagine, glutamine, cystine, serine, threonine, tyrosine) amino acids. Phenylalanine, tryptophan, and tyrosine are sometimes classified as aromatic amino acids. It is reasonable to expect that an isolated replacement of a leucine with an isoleucine or valine, an aspartate with a glutamate, a threonine with a serine, or a similar replacement of an amino acid with a structurally related amino acid will not have a major effect on the binding properties of the resulting molecule, especially if the replacement does not involve an amino acid at a binding site involved in an interaction of the protein. Non-naturally occurring amino acids can also be used to form protein variants of the invention.

[0065] Whether an amino acid change results in a functional protein or polypeptide can readily be determined by assaying biological properties of the disclosed proteins or polypeptides, as described below. Species homologs of human subgenomic polynucleotides and proteins of the invention can also be identified by making suitable probes or primers and screening cDNA expression libraries from other species, such as mice, monkeys, yeast, or bacteria.

[0066] In the case of proteins which are membrane-bound, such as cell surface receptor proteins, soluble forms of the proteins can be obtained by deleting the nucleotide sequences which encode part or all of the intracellular and transmembrane domains of the protein and expressing a fully secreted form of the protein in a host cell. Techniques for identifying intracellular and transmembrane domains, such as homology searches, can be used to identify such domains in proteins of the invention using amino acid and nucleotide sequences disclosed herein.

[0067] Polypeptides consisting of less than full-length proteins of the present invention are also provided. Polypeptides of the invention can be linear or can be cyclized, for example, as described in Saragovi et al., 1992, Bio/Technology 10, 773-778 and McDowell et al., 1992, J. Amer. Chem. Soc. 114, 9245-9253. Polypeptides can be used, for example, as immunogens, diagnostic aids, or therapeutics, and to create fusion proteins, as described below.

[0068] Polypeptide molecules consisting of less than the entire amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38 are also provided. Such polypeptides comprise at least 6, 8, 10, 12, 15, 18, or 20 contiguous amino acids of an amino acid sequence shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38. Polypeptide molecules of the invention can also possess minor amino acid alterations which do not substantially affect the ability of the polypeptides to interact with specific molecules, such as antibodies.

[0069] Derivatives of the polypeptides, such as glycosylated forms, aggregative conjugates with other molecules, and covalent conjugates with unrelated chemical moieties, are also provided. Derivatives also include allelic variants, species variants, and muteins. Covalent derivatives are prepared by linkage of functionalities to groups which are found in the amino acid chain or at the N- or C-terminal residue by means known in the art. Truncations or deletions of regions which do not affect biological function are also encompassed. Truncated or deleted polypeptides can be prepared synthetically or recombinantly, or by proteolytic digestion of purified or partially purified secreted proteins of the invention.

[0070] Fusion proteins comprising at least 6, 8, 10, 12, 15, 18, or 20 contiguous amino acids of the disclosed proteins can also be constructed. Human fusion proteins are useful, inter alia, for generating antibodies against amino acid sequences and for use in various assay systems. For example, fusion proteins can be used to identify proteins which interact with secreted proteins of the invention and influence their function. Physical methods, such as protein affinity chromatography, or library-based assays for protein-protein interactions, such as the yeast two-hybrid or phage display systems, can be used for this purpose. Such methods are well known in the art and can also be used as drug screens. Fusion proteins can also be used to target molecules to a specific location in a cell or to cause a molecule to be secreted or to be anchored in a cellular membrane.

[0071] Fusion proteins of the invention comprise two protein segments which are fused together with a peptide bond. The first protein segment comprises at least 6, 8, 10, 12, 15, 18, or 20 contiguous amino acids selected from an amino acid sequence shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38. The first protein segment can also be a full-length protein (comprising a signal sequence) or a mature protein (lacking a signal sequence). The second protein segment can be a full-length protein or a protein fragment. The second protein or protein fragment can be labeled with a detectable marker, such as a radioactive, chemiluminescent, biotinylated, or fluorescent tag, or can be an enzyme which will generate a detectable product. Enzymes suitable for this purpose, such as β-galactosidase, are well known in the art.

[0072] Techniques for making fusion proteins, either recombinantly or by covalently linking two protein segments, are well known in the art. Fusion proteins comprising amino acid sequences of the invention can also be constructed, for example, using standard recombinant DNA methods to make a DNA construct which comprises contiguous nucleotides selected from SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 and encoding the desired amino acids in proper reading frame with nucleotides encoding the second protein segment.

[0073] Proteins or polypeptides of the invention can be purified free from other components with which they are normally associated in a cell, such as carbohydrates, lipids, subcellular organelles, or other proteins. An isolated protein or polypeptide is at least 90% pure. Preferably, the preparations are 95% or 99% pure. The purity of a preparation can be assessed, for example, by examining electrophoretograms of protein or polypeptide preparations at several pH values and at several polyacrylamide concentrations, as is known in the art.

[0074] Standard biochemical methods can be used to isolate proteins of the invention from tissues which express the proteins or to isolate proteins, polypeptides, or fusion proteins from recombinant host cells into which a DNA construct has been introduced. Methods of protein purification, such as size exclusion chromatography, ammonium sulfate fractionation, ion exchange chromatography, affinity chromatography, crystallization, electrofocusing, or preparative gel electrophoresis, are well known and widely used in the art.

[0075] Alternatively, proteins, fusion proteins, or polypeptides of the invention can be produced by recombinant DNA methods or by synthetic chemical methods. Synthetic chemistry methods, such as solid phase peptide synthesis, can be used to synthesize proteins, fusion proteins, or polypeptides. For production of recombinant proteins, fusion proteins, or polypeptides, coding sequences selected from the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 can be expressed in prokaryotic or eukaryotic host cells using expression systems known in the art. These expression systems include bacterial, yeast, insect, and mammalian cells (see below).

[0076] The resulting expressed protein can then be purified from the culture medium or from extracts of the cultured cells using purification procedures known in the art. For example, for proteins fully secreted into the culture medium, cell-free medium can be diluted with sodium acetate and contacted with a cation exchange resin, followed by hydrophobic interaction chromatography. Using this method, the desired protein, fusion protein, or polypeptide is typically greater than 95% pure. Further purification can be undertaken, using, for example, any of the techniques listed above. Proteins, fusion proteins, or polypeptides can also be tagged with an epitope, such as a “Flag” epitope (Kodak), and purified using an antibody which specifically binds to that epitope.

[0077] It may be necessary to modify a protein produced in yeast or bacteria, for example by phosphorylation or glycosylation of the appropriate sites, in order to obtain a functional protein. Such covalent attachments can be made using known chemical or enzymatic methods.

[0078] Proteins or polypeptides of the invention can also be expressed in cultured cells in a form which will facilitate purification. For example, a secreted protein or polypeptide can be expressed as a fusion protein comprising, for example, maltose binding protein, glutathione-S-transferase, or thioredoxin, and purified using a commercially available kit. Kits for expression and purification of such fusion proteins are available from companies such as New England BioLabs, Pharmacia, and Invitrogen.

[0079] The coding sequences disclosed herein can also be used to construct transgenic animals, such as cows, goats, pigs, or sheep. Female transgenic animals can then produce proteins, polypeptides, or fusion proteins of the invention in their milk. Methods for constructing such animals are known and widely used in the art.

[0080] Isolated proteins, polypeptides, or fusion proteins of the invention can be used to obtain a preparation of antibodies which specifically bind to epitopes comprising amino acid sequences of the invention. Antibodies of the invention can be used, for example, to detect proteins, polypeptides, or fusion proteins of the invention which are secreted into culture medium or to identify tissues or cells which express these molecules. The antibodies can be polyclonal or monoclonal or can be single chain antibodies. Techniques for raising polyclonal and monoclonal antibodies and for constructing single chain antibodies are well known in the art.

[0081] Antibodies of the invention bind specifically to epitopes comprising amino acid sequences of the invention, preferably to epitopes not present on other proteins. Typically a minimum number of contiguous amino acids to encode an epitope is 6, 8, or 10. However, more amino acids can be part of an epitope, for example, at least 15, 25, or 50, especially to form epitopes which involve non-contiguous residues. Specific binding antibodies do not detect other proteins on Western blots of proteins or in immunocytochemical assays. Specific binding antibodies provide a signal at least ten-fold lower than the signal provided with epitopes which do not comprise amino acid sequences of the invention. Antibodies which bind specifically to secreted proteins of the invention include those that bind to mature or full-length proteins, to polypeptides or degradation products, to fusion proteins, or to protein variants. In a preferred embodiment of the invention, the antibodies immunoprecipitate the desired protein, fusion protein, or polypeptide from solution and react with the protein, fusion protein, or polypeptide on Western blots of polyacrylamide gels.

[0082] Techniques for purifying antibodies are those which are available in the art. In a preferred embodiment, antibodies are affinity purified by passing the antibodies over a column to which amino acid sequences of the invention are bound. The bound antibody is then eluted, for example using a buffer with a high salt concentration. Any such technique may be chosen to purify antibodies of the invention.

[0083] The invention also provides DNA constructs, for expressing all or a portion of a protein of the invention in a host cell. The DNA construct comprises a promoter which is functional in the particular host cell selected. The skilled artisan can readily select an appropriate promoter from the large number of cell type-specific promoters known and used in the art. The DNA construct can also contain a transcription terminator which is functional in the host cell.

[0084] The expression construct comprises a polynucleotide segment which encodes all or a portion of a human protein encoded by SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 or a variant thereof The polynucleotide segment is located downstream from the promoter. Transcription of the polynucleotide segment initiates at the promoter. DNA constructs can be linear or circular and can contain sequences, if desired, for autonomous replication.

[0085] The host cell comprising the DNA construct can be any suitable prokaryotic or eukaryotic cell. Expression systems in bacteria include those described in Chang et al., Nature (1978) 275: 615; Goeddel et al., Nature (1979) 281: 544; Goeddel et al., Nucleic Acids Res. (1980) 8: 4057; EP 36,776; U.S. Pat. No. 4,551,433; deBoer et al., Proc. Natl. Acad. Sci. USA (1983) 80: 21-25; and Siebenlist et al., Cell (1980) 20: 269.

[0086] Expression systems in yeast include those described in Hinnen et al., Proc. Natl. Acad. Sci. USA (1978) 75: 1929; Ito et al., J. Bacteriol. (1983) 153: 163; Kurtz et al., Mol. Cell. Biol. (1986) 6: 142; Kunze et al., J. Basic Microbiol.(1985) 25: 141; Gleeson et al., J. Gen. Microbiol. (1986) 132: 3459, Roggenkamp et al., Mol. Gen. Genet. (1986) 202 :302); Das et al., J. Bacteriol. (1984) 158: 1165; De Louvencourt et al., J. Bacteriol. (1983) 154: 737, Van den Berg et al., Bio/Technology (1990) 8: 135; Kunze et al, J. Basic Microbiol. (1985) 25: 141; Cregg et al., Mol. Cell. Biol. (1985) 5: 3376; U.S. Pat. No. 4,837,148; U.S. Pat. No. 4,929,555; Beach and Nurse, Nature (1981) 300: 706; Davidow et al., Curr. Genet. (1985) 10: 380; Gaillardin et al., Curr. Genet. (1985) 10: 49; Ballance et al., Biochem. Biophys. Res. Commun. (1983) 112: 284-289; Tilburn et al., Gene (1983) 26: 205-22;, Yelton et al., Proc. Natl. Acad. Sci. USA (1984) 81: 1470-1474; Kelly and Hynes, EMBO J. (1985) 4: 475479; EP 244,234; and WO 91/00357.

[0087] Expression of heterologous genes in insects can be accomplished as described in U.S. Pat. No. 4,745,051; Friesen et al. (1986) “The Regulation of Baculovirus Gene Expression” in: THE MOLECULAR BIOLOGY OF BACULOVIRUSES (W. Doerfler, ed.); EP 127,839; EP 155,476; Vlak et al., J. Gen. Virol. (1988) 69: 765-776; Miller et al., Ann. Rev. Microbiol. (1988) 42: 177; Carbonell et al., Gene (1988) 73: 409; Maeda et al., Nature (1985) 315: 592-594; Lebacq-Verheyden et al., Mol. Cell. Biol. (1988) 8: 3129; Smith et al., Proc. Natl. Acad. Sci. USA (1985) 82: 8404; Miyajima et al., Gene (1987) 58: 273; and Martin et al., DNA (1988) 7:99. Numerous baculoviral strains and variants and corresponding permissive insect host cells from hosts are described in Luckow et al., Bio/Technology (1988) 6: 47-55, Miller et al., in GENERIC ENGINEERING (Setlow, J. K. et al eds.), Vol. 8 (Plenum Publishing, 1986), pp. 277-279; and Maeda et al., Nature, (1985) 315: 592-594.

[0088] Mammalian expression can be accomplished as described in Dijkema et al., EMBO J. (1985) 4: 761; Gorman et al., Proc. Natl. Acad. Sci. USA (1982b) 79: 6777; Boshart et al., Cell (1985) 41: 521; and U.S. Pat. No. 4,399,216. Other features of mammalian expression can be facilitated as described in Ham and Wallace, Meth. Enz. (1979) 58: 44; Barnes and Sato, Anal. Biochem. (1980) 102: 255; U.S. Pat. No. 4,767,704; U.S. Pat. No. 4,657,866; U.S. Pat. No. 4,927,762; U.S. Pat. No. 4,560,655; WO 90/103430, WO 87/00195, and U.S. RE 30,985.

[0089] DNA constructs of the invention can be introduced into host cells using any technique known in the art. These techniques include transferrin-polycation-mediated DNA transfer, transfection with naked or encapsulated nucleic acids, liposome-mediated cellular fusion, intracellular transportation of DNA-coated latex beads, protoplast fusion, viral infection, electroporation, and calcium phosphate-mediated transfection.

[0090] Alternatively, expression of an endogenous gene encoding a protein of the invention can be manipulated by introducing by homologous recombination a DNA construct comprising a transcription unit in frame with the endogenous gene, to form a homologously recombinant cell comprising the transcription unit. The transcription unit comprises a targeting sequence, a regulatory sequence, an exon, and an unpaired splice donor site. The new transcription unit can be used to turn the endogenous gene on or off as desired. This method of affecting endogenous gene expression is taught in U.S. Pat. No. 5,641,670, which is incorporated herein by reference.

[0091] The targeting sequence is a segment of at least 10, 12, 15, 20, or 50 contiguous nucleotides selected from the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19. The transcription unit is located upstream to a coding sequence of the endogenous gene. The exogenous regulatory sequence directs transcription of the coding sequence of the endogenous gene.

[0092] Secreted proteins of the invention have a variety of uses. For example, secreted proteins can be used in assays to determine biological activities, such as cytokine, cell proliferation, or cellular differentiation activities, tissue growth or regeneration, activin or inhibin activity, chemotactic or chemokinetic activity, hemostatic or thrombolytic activity, receptor/ligand activity, tumor inhibition, or anti-inflammatory activity. Assays for these activities are known in the art and are disclosed, for example, in U.S. Pat. No. 5,654,173, which is incorporated herein by reference.

[0093] Proteins of the invention can also be used as biomarkers, to identify tissues or cell types which express the proteins, or a stage- or disease-specific alteration in protein expression. Proteins of the invention can be used in protein interaction assays, to identify ligands or binding proteins. Compounds which affect the biological activities of the secreted proteins or their ability to interact with specific ligands can be identified using proteins of the invention in screening assays. Proteins and antibodies of the invention can also be used to design diagnostic tests and therapeutic compositions for diseases which may be associated with altered expression of these proteins. Fusion proteins comprising, for example, signal sequences or transmembrane domains of the disclosed proteins, can be used to target other protein domains to cellular locations in which the domains are not normally found, such as bound to a cellular membrane or secreted extracellularly.

[0094] Further objects, features, and advantages of the present invention will readily occur to the skilled artisan provided with the disclosure above.

SYNOPSIS OF THE INVENTION

[0095] 1. An isolated and purified human protein having an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38.

[0096] 2. An isolated and purified human protein having an amino acid sequence which is at least 85% identical to an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38.

[0097] 3. The isolated and purified human protein of item 2 wherein the amino acid sequence is at least 90% identical.

[0098] 4. The isolated and purified human protein of item 2 wherein the amino acid sequence is at least 95% identical.

[0099] 5. The isolated and purified human protein of item 2 wherein the amino acid sequence is at least 98% identical.

[0100] 6. An isolated and purified human polypeptide comprising at least 6 contiguous amino acids of an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and

[0101]38.

[0102] 7. A fusion protein comprising a first protein segment and a second protein segment fused together by means of a peptide bond, wherein the first protein segment consists of at least 6 contiguous amino acids selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38.

[0103] 8. A preparation of antibodies which specifically bind to the human protein of item 1.

[0104] 9. The preparation of antibodies of item 8 wherein the antibodies are monoclonal.

[0105] 10. The preparation of antibodies of item 8 wherein the antibodies are polyclonal.

[0106] 11. The preparation of antibodies of item 8 wherein the antibodies are single chain antibodies.

[0107] 12. An isolated and purified subgenomic polynucleotide having a nucleotide sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0108] 13. An isolated and purified subgenomic polynucleotide consisting of at least 10 contiguous nucleotides of a nucleotide sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0109] 14. An isolated gene corresponding to a cDNA sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19.

[0110] 15. A DNA construct for expressing all or a portion of a human protein having an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38, comprising:

[0111] a promoter; and

[0112] a polynucleotide segment encoding at least 6 contiguous amino acids of the human protein, wherein the polynucleotide segment is located downstream from the promoter, wherein transcription of the polynucleotide segment initiates at or 3′ to the promoter.

[0113] 16. A host cell comprising a DNA construct comprising:

[0114] a promoter; and

[0115] a polynucleotide segment encoding at least 6 contiguous amino acids of a human protein having an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38, wherein the polynucleotide segment is located downstream from the pormoter and wherein transcription of the polynucleotide segment initiates at or 3′ to the promoter.

[0116] 17. A homologously recombinant cell having incorporated therein a new transcription initiation unit, wherein the new transcription initiation unit comprises in 5′ to 3′ order:

[0117] (a) an exogenous regulatory sequence;

[0118] (b) an exogenous exon; and

[0119] (c) a splice donor site,

[0120] wherein the transcription initiation unit is located upstream to a coding sequence of a gene, wherein the gene comprises a nucleotide sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19, and wherein the exogenous regulatory sequence controls transcription of the coding sequence of the gene.

[0121] 18. A method of producing a human protein, comprising the steps of:

[0122] growing a culture of a cell comprising a DNA construct comprising (1) a promoter and (2) a polynucleotide segment encoding at least 6 contiguous amino acids of a human protein having an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38, wherein the polynucleotide segment is located downstream from the promoter and wherein transcription of the polynucleotide segment initiates at or 3′ to the promoter; and;

[0123] purifying the protein from the culture.

[0124] 19. A method of producing a human protein, comprising the steps of:

[0125] growing a culture of a homologously recombinant cell having incorporated therein a new transcription initiation unit, wherein the new transcription initiation unit comprises in 5′ to 3′ order:

[0126] (a) an exogenous regulatory sequence;

[0127] (b) an exogenous exon; and

[0128] (c) a splice donor site,

[0129] wherein the transcription initiation unit is located upstream to a coding sequence of a gene, wherein the gene comprises a nucleotide sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 and wherein the exogenous regulatory sequence controls transcription of the coding sequence of the gene; and

[0130] purifying the protein from the culture.

[0131] 20. A method of identifying a secreted polypeptide which is modified by rough microsomes, comprising the steps of:

[0132] transcribing in vitro a population of cDNA molecules whereby a population of cRNA molecules is formed;

[0133] translating a first portion of the population of cRNA molecules in vitro in the absence of rough microsomes whereby a first population of polypeptides is formed;

[0134] translating a second portion of the population of cRNA molecules in vitro in the presence of rough rnicrosomes whereby a second population of polypeptides is formed;

[0135] comparing the first population of polypeptides with the second population of polypeptides; and

[0136] detecting polypeptide members of the second population which have been modified by the rough microsomes.

[0137] 21. The method of item 20 wherein the population of cDNA molecules is synthesized by reverse transcription of a population of mRNA molecules.

[0138] 22. The method of item 21 wherein the mRNA molecules are isolated from a mammal.

[0139] 23. The method of item 22 wherein the MRNA molecules are isolated from a human.

[0140] 24. The method of item 20 wherein the population of cDNA molecules is obtained from a cDNA library.

[0141] 25. The method of item 24 wherein the cDNA library is derived from a mammalian genome.

[0142] 26. The method of item 25 wherein the CDNA library is derived from a human genome.

0 SEQUENCE LISTING (1) GENERAL INFORMATION: (iii) NUMBER OF SEQUENCES: 38 (2) INFORMATION FOR SEQ ID NO: 1: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2063 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ix) FEATURE: (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 1: GAATTCGGCA CGAGGCCTCA GTCTTCCAGG GCGGCGGTGG GTGTCCGCTT CTCTCTGCTC 60 TTCGACTGCA CCGCACTCGC GCGTGACCCT GACTCCCCCT AGTCAGCTCA GCGGTGCTGC 120 CATGGCGTGG CGGCGGCGCG AAGCCGGCGT CGGGGCTCGC GGCGTGTTGG CTCTGGCGTT 180 GCTCGCCCTG GCCCTGTGCG TGCCCGGGGC CCGGGGCCGG GCTCTCGAGT GGTTCTCGGC 240 CGTGGTAAAC ATCGAGTACG TGGACCCGCA GACCAACCTG ACGGTGTGGA GCGTCTCGGA 300 GAGTGGCCGC TTCGGCGACA GCTCGCCCAA GGAGGGCGCG CATGGCCTGG TGGGCGTCCC 360 GTGGGCGCCC GGCGGAGACC TCGAGGGCTG CGCGCCCGAC ACGCGCTTCT TCGTGCCCGA 420 GCCCGGCGGC CGAGGGGCCG CGCCCTGGGT CGCCCTGGTG GCTCGTGGGG GCTGCACCTT 480 CAAGGACAAG GTGCTGGTGG CGGCGCGGAG GAACGCCTCG GCCGTCGTCC TCTACAATGA 540 GGAGCGCTAC GGGAACATCA CCTTGCCCAT GTCTCACGCG GGAACAGGAA ATATAGTGGT 600 CATTATGATT AGCTATCCAA AAGGAAGAGA AATTTTGGAG CTGGTGCAAA AAGGAATTCC 660 AGTAACGATG ACCATAGGGG TTGGCACCCG GCATGTACAG GAGTTCATCA GCGGTCAGTC 720 TGTGGTGTTT GTGGCCATTG CCTTCATCAC CATGATGATT ATCTCGTTAG CCTGGCTAAT 780 ATTTTACTAT ATACAGCGTT TCCTATATAC TGGCTCTCAG ATTGGAAGTC AGAGCCATAG 840 AAAAGAAACT AAGAAAGTTA TTGGCCAGCT TCTACTTCAT ACTGTAAAGC ATGGAGAAAA 900 GGGAATTGAT GTTGATGCTG AAAATTGTGC AGTGTGTATT GAAAATTTCA AAGTAAAGGA 960 TATTATTAGA ATTCTGCCAT GCAAGCATAT TTTTCATAGA ATATGCATTG ACCCATGGCT 1020 TTTGGATCAC CGAACATGTC CAATGTGTAA ACTTGATGTC ATCAAAGCCC TAGGATATTG 1080 GGGAGAGCCT GGGGATGTAC AGGAGATGCC TGCTCCAGAA TCTCCTCCTG GAAGGGATCC 1140 AGCTGCAAAT TTGAGTCTAG CTTTACCAGA TGATGACGGA AGTGATGACA GCAGTCCACC 1200 ATCAGCCTCC CCTGCTGAAT CTGAGCCACA GTGTGATCCC AGCTTTAAAG GAGATGCAGG 1260 AGAAAATACG GCATTGCTAG AAGCCGGCAG GAGTGACTCT CGGCATGGAG GACCCATCTC 1320 CTAGCACACG TGCCCACTGA AGTGGCACCA ACAGAAGTTT GGCTTGAACT AAAGGACATT 1380 TTATTTTTTT TACTTTAGCA CATAATTTGT ATATTTGAAA ATAATGTATA TTATTTTACC 1440 TATTAGATTC TGATTTGATA TACAAAGGAC TAAGATATTT TCTTCTTGAA GAGACTTTTC 1500 GATTAGTCCT CATATATTTA TCTACTAAAA TAGAGTGTTT ACCATGAACA GTGTGTTGCT 1560 TCAGACTATT ACAAAGACAA CTGGGGCAGG TACTCTAATA TAAAGGACAG GTGGTGTTTC 1620 TAAATAATTG GCTGCTATGG TTCTGTAAAA ACCAGTTAAT TCTATTTTTC AAGGTTTTTG 1680 GCAAAGCACA TCAATGTTAG ACTAGTTGAA GTGGAATTGT ATAATTCAAT TCGATAATTG 1740 ATCTCATGGG CTTTCCCTGG AGGAAAGGTT TTTTTTGTTG TTTTTTTTTT AAGAACTTGA 1800 AACTTGTAAA CTGAGATGTC TGTAGCTTTT TTGCCCATCT GTAGTGTATG TGAAGATTCT 1860 AAAACCTGAG AGCACTTTTT CTTTGTTTAG AATTATGAGA AAGGCACTAG ATGACTTTAG 1920 GATTTGCATT TTTCCCTTTA TTGCCTCATT TCTTGTGACG CCTTGTTGGG GAGGGAAATC 1980 TGTTTATTTT TTCCTACAAA TAAAAAGCTA AGATTCTATA TCGCAAAAAA AAAAAAAAAA 2040 AAAAAAAAAA TTCCTGCGGC CGC 2063 (2) INFORMATION FOR SEQ ID NO: 2: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1328 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 2: GAATTCGGCA CGAGGTAGGC AAGGGATAAA AAGGCACCTA AGGCCCTTTT GCAATAAGAA 60 GCCAGATGGA TAAAGGAAGT GCTGGTCACC CTGGAGGTGT ACTGGTTTGG GGAAGGTCCC 120 CGGCCCCCAC AGCCCTCTGG GGAGCCTCAC CCTGGCTCTC CCCACTCACC TCAGCCCTCA 180 GGCAGCCCCT CCACAGGGCC CCTCTCCTGC CTGGACAGCT CTGCTGGTCT CCCCGTCCCC 240 TGGAGAAGAA CAAGGCCATG GGTCGGCCCC TGCTGCTGCC CCTGCTGCTC CTGCTGCAGC 300 CGCCAGCATT TCTGCAGCCT GGTGGCTCCA CAGGATCTGG TCCAAGCTAC CTTTATGGGG 360 TCACTCAACC AAAACACCTC TCAGCCTCCA TGGGTGGCTC TGTGGAAATC CCCTTCTCCT 420 TCTATTACCC CTGGGAGTTA GCCATAGTTC CCAACGTGAG AATATCCTGG AGACGGGGCC 480 ACTTCCACGG GCAGTCCTTC TACAGCACAA GGCCGCCTTC CATTCACAAG GATTATGTGA 540 ACCGGCTCTT TCTGAACTGG ACAGAGGGTC AGGAGAGCGG CTTCCTCAGG ATCTCAAACC 600 TGCGGAAGGA GGACCAGTCT GTGTATTTCT GCCGAGTCGA GCTGGACACC CGGAGATCAG 660 GGAGGCAGCA GTTGCAGTCC ATCAAGGGGA CCAAACTCAC CATCACCCAG GCTGTCACAA 720 CCACCACCAC CTGGAGGCCC AGCAGCACAA CCACCATAGC CGGCCTCAGG GTCACAGAAA 780 GCAAAGGGCA CTCAGAATCA TGGCACCTAA GTCTGGACAC TGCCATCAGG GTTGCATTGG 840 CTGTCGCTGT GCTCAAAACT GTCATTTTGG GACTGCTGTG CCTCCTCCTC CTGTGGTGGA 900 GGAGAAGGAA AGGTAGCAGG GCGCCAAGCA GTGACTTCTG ACCAACAGAG TGTGGGGAGA 960 AGGGATGTGT ATTAGCCCCG GAGGACGTGA TGTGAGACCC GCTTGTGAGT CCTCCACACT 1020 CGTTCCCCAT TGGCAAGATA CATGGAGAGC ACCCTGAGGA CCTTTAAAAG GCAAAGCCGC 1080 AAGGCAGAAG GAGGCTGGGT CCCTGAATCA CCGACTGGAG GAGAGTTACC TACAAGAGCC 1140 TTCATCCAGG AGCATCCACA CTGCAATGAT ATAGGAATGA GGTCTGAACT CCACTGAATT 1200 AAACCACTGG CATTTGGGGG CTGTTTATTA TAGCAGTGCA AAGAGTTCCT TTATCCTCCC 1260 CAAGGATGGA AAAATACAAT TTATTTTGCT TACCATAAAA AAAAAAAAAA AAAAATTCCT 1320 GCGGCCGC 1328 (2) INFORMATION FOR SEQ ID NO: 3: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1689 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 3: GAATTCGGCA CGAGGGCAAG ATTCGATACA AAACCAATGA ACCTGTGTGG GAGGAAAACT 60 TCACTTTCTT CATTCACAAT CCCAAGCGCC AGGACCTTGA AGTTGAGGTC AGAGACGAGC 120 AGCACCAGTG TTCCCTGGGG AACCTGAAGG TCCCCCTCAG CCAGCTGCTC ACCAGTGAGG 180 ACATGACTGT GAGCCAGCGC TTCCAGCTCA GTAACTCGGG TCCAAACAGC ACCATCAAGA 240 TGAAGATTGC CCTGCGGGTG CTCCATCTCG AAAAGCGAGA AAGGCCTCCA GACCACCAAC 300 ACTCAGCTCA AGTCAAACGT CCCTCTGTGT CCAAAGAGGG GAGGAAAACA TCCATCAAAT 360 CTCATATGTC TGGGTCTCCA GGCCCTGGTG GCAGCAACAC AGCTCCATCC ACACCAGTCA 420 TTGGGGGCAG TGATAAGCCT GGTATGGAAG AAAAGGCCCA GCCCCCTGAG GCCGGCCCTC 480 AGGGGCTGCA CGACCTGGGC AGAAGCTCCT CCAGCCTCCT GGCCTCCCCA GGCCACATCT 540 CAGTCAAGGA GCCGACCCCC AGCATCGCCT CGGACATCTC GCTGCCCATC GCCACCCAGG 600 AGCTGCGGCA AAGGCTGAGG CAGCTGGAAA ACGGGACGAC CCTGGGACAG TCTCCACTGG 660 GGCAGATCCA GCTGACCATC CGGCACAGCT CGCAGAGAAA CAAGCTTATC GTGGTCGTGC 720 ATGCCTGCAG AAACCTCATT GCCTTCTCTG AAGACGGCTC TGACCCCTAT GTCCGCATGT 780 ATTTATTACC AGACAAGAGG CGGTCAGGAA GGAGGAAAAC ACACGTGTCA AAGAAAACAT 840 TAAATCCAGT GTTTGATCAA AGCTTTGATT TCAGTGTTTC GTTACCAGAA GTGCAGAGGA 900 GAACGCTCGA CGTTGCCGTG AAGAACAGTG GCGGCTTCCT GTCCAAAGAC AAAGGGCTCC 960 TTGGCAAAGT ATTGGTTGCT CTGGCATCTG AAGAACTTGC CAAAGGCTGG ACCCAGTGGT 1020 ATGACCTCAC GGAAGATGGG ACGAGGCCTC AGGCGATGAC ATAGCCGCAG CAGGCAGGAG 1080 GCGTCCTCTT CAGCGTAGCT CTCCACCTCT ACCCGGAACA CACCCTCTCA CAGACGTACC 1140 AATGTTATTT TTATAATTTC ATGGATTTAG TTATACATAC CTTAATAGTT TTATAAAATT 1200 GTTGACATTT CAGGCAAATT TGGCCAATAT TATCATTGAA TTTTCTGTGT TGGATTTCCT 1260 CTAGGATTTC GCCAGTTCCT ACAACGTGCA GTAGGGCGGC GGTAGCTCTT GTGTCTGTGG 1320 ACTCTGCTCA GCTGTGTCCG TAGGAGTCGG ATGTGTCTGT GCTTTATTAT GGCCTTGTTT 1380 ATATATCACT GAGGTATACT ATGCCATGTA AATAGACTAT TTTTTATAAT CTTAACATGC 1440 TGGTTTAAAT TCAGAAGGAA ATAGATCAAG GAAATATATA TATTTTCTTC TAAAACTTAT 1500 TAAATTCGTG TGACAAATAA TCATTTTCAT CTTGGCAGCA AAAAGTTCTC AGTGACCTAT 1560 TTTGTGGTGT TTCTTTTTGA AAAGAAAAGC TGAAATATTA TTAAATGCTA GTATGTTTCT 1620 GCCCATTATG AAAGATGAAA TAAAGTATTC AAAATATTAA AAAAAAAAAA AAAAAATTCC 1680 TGCGGCCGC 1689 (2) INFORMATION FOR SEQ ID NO: 4: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1505 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 4: GAATTCGGCA CGAGGAGCAG ATCTGCAAGA GTTTCGTTTA TGGAGGCTGC TTGGGCAACA 60 AGAACAACTA CCTTCGGGAA GAAGAGTGCA TTCTAGCCTG TCGGGGTGTG CAAGGTGGGC 120 CTTTGAGAGG CAGCTCTGGG GCTCAGGCGA CTTTCCCCCA GGGCCCCTCC ATGGAAAGGC 180 GCCATCCAGT GTGCTCTGGC ACCTGTCAGC CCACCCAGTT CCGCTGCAGC AATGGCTGCT 240 GCATCGACAG TTTCCTGGAG TGTGACGACA CCCCCAACTG CCCCGACGCC TCCGACGAGG 300 CTGCCTGTGA AAAATACACG AGTGGCTTTG ACGAGCTCCA GCGCATCCAT TTCCCCAGCG 360 ACAAAGGGCA CTGCGTGGAC CTGCCAGACA CAGGACTCTG CAAGGAGAGC ATCCCGCGCT 420 GGTACTACAA CCCCTTCAGC GAACACTGCG CCCGCTTTAC CTATGGTGGT TGTTACGGCA 480 ACAAGAACAA CTTTGAGGAA GAGCAGCAGT GCCTCGAGTC TTGTCGCGGC ATCTCCAAGA 540 AGGATGTGTT TGGCCTGAGG CGGGAAATCC CCATTCCCAG CACAGGCTCT GTGGAGATGG 600 CTGTCGCAGT GTTCCTGGTC ATCTGCATTG TGGTGGTGGT AGCCATCTTG GGTTACTGCT 660 TCTTCAAGAA CCAGAGAAAG GACTTCCACG GACACCACCA CCACCCACCA CCCACCCCTG 720 CCAGCTCCAC TGTCTCCACT ACCGAGGACA CGGAGCACCT GGTCTATAAC CACACCACGC 780 GGCCCCTCTG AGCCTGGGTC TCACCGGCTC TCACCTGGCC CTGCTTCCTG CTTGCCAAGG 840 CAGAGGCCTG GGCTGGGAAA AACTTTGGAA CCAGACTCTT GCCTGTTTCC CAGGCCCACT 900 GTGCCTCAGA GACCAGGGCT CCAGCCCCTC TTGGAGAAGT CTCAGCTAAG CTCACGTCCT 960 GAGAAAGCTC AAAGGTTTGG AAGGAGCAGA AAACCCTTGG GCCAGAAGTA CCAGACTAGA 1020 TGGACCTGCC TGCATAGGAG TTTGGAGGAA GTTGGAGTTT TGTTTCCTCT GTTCAAAGCT 1080 GCCTGTCCCT ACCCCATGGT GCTAGGAAGA GGAGTGGGGT GGTGTCAGAC CCTGGAGGCC 1140 CCAACCCTGT CCTCCCGAGC TCCTCTTCCA TGCTGTGCGC CCAGGGCTGG GAGGAAGGAC 1200 TTCCCTGTGT AGTTTGTGCT GTAAAGAGTT GCTTTTTGTT TATTTAATGC TGTGGCATGG 1260 GTGAAGAGGA GGGGAAGAGG CCTGTTTGGC CTCTCTATCC TCTCTTCCTC TTCCCCCAAG 1320 ATTGAGCTCT CTGCCCTTGA TCAGCCCCAC CCTGGCCTAG ACCAGCAGAC AGAGCCAGGA 1380 GAAGCTCAGC TGCATTCCGC AGCCCCCACC CCCAAGGTTC TCCAACATCA CAGCCCAGCC 1440 CGCCCACTGG GTAATAAAAG TGGTTTGTGG AAAAAAAAAA AAAAAAAAAA AAGTCCTGCG 1500 GCCGC 1505 (2) INFORMATION FOR SEQ ID NO: 5: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 2002 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 5: GAATTCGGCA CGAGGGCCAT GGCCGGGCTA TCCCGCGGGT CCGCGCGCGC ACTGCTCGCC 60 GCCCTGCTGG CGTCGACGCT GTTGGCGCTG CTCGTGTCGC CCGCGCGGGG TCGCGGCGGC 120 CGGGACCACG GGGACTGGGA CGAGGCCTCC CGGCTGCCGC CGCTACCACC CCGCGAGGAC 180 GCGGCGCGCG TGGCCCGCTT CGTGACGCAC GTCTCCGACT GGGGCGCTCT GGCCACCATC 240 TCCACGCTGG AGGCGGTGCG CGGCCGGCCC TTCGCCGACG TCCTCTCGCT CAGCGACGGG 300 CCCCCGGGCG CGGGCAGCGG CGTGCCCTAT TTCTACCTGA GCCCGCTGCA GCTCTCCGTG 360 AGCAACCTGC AGGAGAATCC ATATGCTACA CTGACCATGA CTTTGGCACA GACCAACTTC 420 TGCAAGAAAC ATGGATTTGA TCCACAAAGT CCCCTTTGTG TTCACATAAT GCTGTCAGGA 480 ACTGTGACCA AGGTGAATGA AACAGAAATG GATATTGCAA AGCATTCGTT ATTCATTCGA 540 CACCCTGAGA TGAAAACCTG GCCTTCCAGC CATAATTGGT TCTTTGCTAA GTTGAATATA 600 ACCAATATCT GGGTCCTGGA CTACTTTGGT GGACCAAAAA TCGTGACACC AGAAGAATAT 660 TATAATGTCA CAGTTCAGTG AAGCAGACTG TGGTGAATTT AGCAACACTT ATGAAGTTTC 720 TTAAAGTGGC TCATACACAC TTAAAAGGCT TAATGTTTCT CTGGAAAGCG TCCCAGAATA 780 TTAGCCAGTT TTCTGTCACA TGCTGGTTTG TTTGCTTGCT TGTTTACTTG CTTGTTTACC 840 AATAGAGTTG ACCTGTTATT GGATTTCCTG GAAGATGTGG TAGCTACTTT TTTCCTATTT 900 TGAAGCCATT TTCGTAGAGA AATATCCTTC ACTATAATCA AATAAGTTTT GTCCCATCAA 960 TTCCAAAGAT GTTTCCAGTG GTGCTCTTGA AGAGGAATGA GTACCAGTTT TAAATTGCCC 1020 ATTGGCATTT GAAGGTAGTT GAGTATGTGT TCTTTATTCC TAGAAGCCAC TGTGCTTGGT 1080 AGAGTGCATC ACTCACCACA GCTGCCTCTT GAGCTGCCTG AGCCTGGTGC AAAAGGATTG 1140 GCCCCCATTA TGGTGCTTCT GAATAAATCT TGCCAAGATA GACAAACAAT GATGAAACTC 1200 AGATGGAGCT TCCTACTCAT GTTGATTTAT GTCTCACAAT CCTGGGTATT GTTAATTCAA 1260 CATAGGGTGA AACTATTTCT GATAAAGAAC TTTTGAAAAA CTTTTTATAC TCTAAAGTGA 1320 TACTCAGAAC AAAAGAAAGT CATAAAACTC CTGAATTTAA TTTCCCCACC TAAGTCGAGA 1380 CAGTATTATC AAAACACATG TGCACACAGA TTATTTTTTG GCTCCAAAAC TGGATTGCAA 1440 AAGAAAGAGG AGAGATATTT TGTGTGTTCC TGGTATTCTT TTATAAGTAA AGTTACCCAG 1500 GCATGGACCA GCTTCAGCCA GGGACAAAAT CCCCTCCCAA ACCACTCTCC ACAGCTTTTT 1560 AAAAATACTT CTACTCTTAA CAATTACCTA AGGTTCCTTC AAACCCCCCC AACTCTTAAT 1620 AGCTTCTAGT GCTGCTACAA TCTAAGTCAG GTCACCAGAG GGAAGAGAAC ATGGCATTAA 1680 AAGAATCACA TCTTCAGAAG AGAAGACACT AATATTATTA CCCATATACA TGATTTCAGA 1740 AGATGACATA AGATTCCTCT TAAAGAGGAA ATGTCAGGAA TCAAGCCACT GAATCCTTAA 1800 AGAGAAAAGT TGAATATGAG TCATTGTGTC TGAAAACTGC AAAGTGAACT TAACTGAGAT 1860 CCAGCAAACA GGTTCTGTTT AAGAAAAATA ATTTATACTA AATTTAGTAA AATGGACTTC 1920 TTATTCAAAG CATCAATAAT TAAAAGAATT ATTTTAAAAA AAAAAAAAAA AAAAAAAAAA 1980 AAAAAAAAAT TCCTGCGGCC GC 2002 (2) INFORMATION FOR SEQ ID NO: 6: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1322 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 6: GAATTCGGCA CGAGGGCCAC GACTCTGCTG GCATTTCTTC TATAGCCACT GGAATCTGAT 60 CCTGATTGTC TTCCACTACT ACCAGGCCAT CACCACTCCG CCTGGGTACC CACCCCAGGG 120 CAGGAATGAT ATCGCCACCG TCTCCATCTG TAAGAAGTGC ATTTACCCCA AGCCAGCCCG 180 AACACACCAC TGCAGCATCT GCAACAGGTG TGTGCTGAAG ATGGATCACC ACTGCCCCTG 240 GCTAAACAAT TGTGTGGGCC ACTATAACCA TCGGTACTTC TTCTCTTTCT GCTTTTTCAT 300 GACTCTGGGC TGTGTCTACT GCAGCTATGG AAGTTGGGAC CTTTTCCGGG AGGCTTATGC 360 TGCCATTGAG AAAATGAAAC AGCTCGACAA GAACAAACTA CAGGCGGTTG CCAACCAGAC 420 TTATCACCAG ACCCCACCAC CCACCTTCTC CTTTCGAGAA AGGATGACTC ACAAGAGTCT 480 TGTCTACCTC TGGTTCCTGT GCAGTTCTGT GGCACTTGCC CTGGGTGCCC TAACTGTATG 540 GCATGCTGTT CTCATCAGTC GAGGTGAGAC TAGCATCGAA AGGCACATCA ACAAGAAGGA 600 GAGACGTCGG CTACAGGCCA AGGGCAGAGT ATTTAGGAAT CCTTACAACT ACGGCTGCTT 660 GGACAACTGG AAGGTATTCC TGGGTGTGGA TACAGGAAGG CACTGGCTTA CTCGGGTGCT 720 CTTACCTTCT ACTCACTTGC CCCATGGGAA TGGAATGAGC TGGGAGCCCC CTCCCTGGGT 780 GACTGCTCAC TCAGCCTCTG TGATGGCAGT GTGAGCTGGA CTGTGTCAGC CACGACTCGA 840 GCACTCATTC TGCTCCCTAT GTTATTTCAA GGGCCTCCAA GGGCAGCTTT TCTCAGAATC 900 CTTGATCAAA AAGAGCCAGT GGGCCTGCCT TAGGGTACCA TGCAGGACAA TTCAAGGACC 960 AGCCTTTTTA CCACTGCAGA AGAAAGACAC AATGTGGAGA AATCTTAGGA CTGACATCCC 1020 TTTACTCAGG CAAACAGAAG TTCCAACCCC AGACTAGGGG TCAGGCAGCT AGCTACCTAC 1080 CTTGCCCAGT GCTGACCCGG ACCTCCTCCA GGATACAGCA CTGGAGTTGG CCACCACCTC 1140 TTCTACTTGC TGTCTGAAAA AACACCTGAC TAGTACAGCT GAGATCTTGG CTTCTCAACA 1200 GGGCAAAGAT ACCAGGCCTG CTGCTGAGGT CACTGCCACT TCTCACATGC TGCTTAAGGG 1260 AGCACAAATA AAGGTATTCG ATTTTTAAAA AAAAAAAAAA AAAAAAAAAT TCCTGCGGCC 1320 GC 1322 (2) INFORMATION FOR SEQ ID NO: 7: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1573 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 7: GAATTCGGCA CGAGGAGCCT GCCTTCATCT AGGATGGCTC CTCTGGGCAT GCTGCTTGGG 60 CTGCTGATGG CCGCCTGCTT CACCTTCTGC CTCAGTCATC AGAACCTGAA GGAGTTTGCC 120 CTGACCAACC CAGAGAAGAG CAGCACCAAA GAAACAGAGA GAAAAGAAAC CAAAGCCGAG 180 GAGGAGCTGG ATGCCGAAGT CCTGGAGGTG TTCCACCCGA CGCATGAGTG GCAGGCCCTT 240 CAGCCAGGGC AGGCTGTCCC TGCAGGATCC CACGTACGGC TGAATCTTCA GACTGGGGAA 300 AGAGAGGCAA AACTCCAATA TGAGGACAAG TTCCGAAATA ATTTGAAAGG CAAAAGGCTG 360 GATATCAACA CCAACACCTA CACATCTCAG GATCTCAAGA GTGCACTGGC AAAATTCAAG 420 GAGGGGGCAG AGATGGAGAG TTCAAAGGAA GACAAGGCAA GGCAGGCTGA GGTAAAGCGG 480 CTCTTCCGCC CCATTGAGGA ACTGAAGAAA GACTTTGATG AGCTGAATGT TGTCATTGAG 540 ACTGACATGC AGATCATGGT ACGGCTGATC AACAAGTTCA ATAGTTCCAG CTCCAGTTTG 600 GAAGAGAAGA TTGCTGCGCT CTTTGATCTT GAATATTATG TCCATCAGAT GGACAATGCG 660 CAGGACCTGC TTTCCTTTGG TGGTCTTCAA GTGGTGATCA ATGGGCTGAA CAGCACAGAG 720 CCCCTCGTGA AGGAGTATGC TGCGTTTGTG CTGGGCGCTG CCTTTTCCAG CAACCCCAAG 780 GTCCAGGTGG AGGCCATCGA AGGGGGAGCC CTGCAGAAGC TGCTGGTCAT CCTGGCCACG 840 GAGCAGCCGC TCACTGCAAA GAAGAAGGTC CTGTTTGCAC TGTGCTCCCT GCTGCGCCAC 900 TTCCCCTATG CCCAGCGGCA GTTCCTGAAG CTCGGGGGGC TGCAGGTCCT GAGGACCCTG 960 GTGCAGGAGA AGGGCACGGA GGTGCTCGCC GTGCGCGTGG TCACACTGCT CTACGACCTG 1020 GTCACGGAGA AGATGTTCGC CGAGGAGGAG GCTGAGCTGA CCCAGGAGAT GTCCCCAGAG 1080 AAGCTGCAGC AGTATCGCCA GGTACACCTC CTGCCAGGCC TGTGGGAACA GGGCTGGTGC 1140 GAGATCACGG CCCACCTCCT GGCGCTGCCC GAGCATGATG CCCGTGAGAA GGTGCTGCAG 1200 ACACTGGGCG TCCTCCTGAC CACCTGCCGG GACCGCTACC GTCAGGACCC CCAGCTCGGC 1260 AGGACACTGG CCAGCCTGCA GGCTGAGTAC CAGGTGCTGG CCAGCCTGGA GCTGCAGGAT 1320 GGTGAGGACG AGGGCTACTT CCAGGAGCTG CTGGGCTCTG TCAACAGCTT GCTGAAGGAG 1380 CTGAGATGAG GCCCCACACC AGGACTGGAC TGGGATGCCG CTAGTGAGGC TGAGGGGTGC 1440 CAGCGTGGGT GGGCTTCTCA GGCAGGAGGA CATCTTGGCA GTGCTGGCTT GGCCATTAAA 1500 TGGAAACCTG AAGGCCAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA 1560 TTCCTGCGGC CGC 1573 (2) INFORMATION FOR SEQ ID NO: 8: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1185 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 8: GAATTCGGCA CGAGGGGGCT TTAAGGGACA GCTGAGCCGG CAGGTGGCAG ATCAGATGTG 60 GCAGGCTGGG AAAAGACAAG CCTCCAGGGC CTTCAGCTTG TACGCCAACA TCGACATCCT 120 CAGACCCTAC TTTGATGTGG AGCCTGCTCA GGTGCGAAGC AGGCTCCTGG AGTCCATGAT 180 CCCTATCAAG ATGGTCAACT TCCCCCAGAA AATTGCAGGT GAACTCTATG GACCTCTCAT 240 GCTGGTCTTC ACTCTGGTTG CTATCCTACT CCATGGGATG AAGACGTCTG ACACTATTAT 300 CCGGGAGGGC ACCCTGATGG GCACAGCCAT TGGCACCTGC TTCGGCTACT GGCTGGGAGT 360 CTCATCCTTC ATTTACTTCC TTGCCTACCT GTGCAACGCC CAGATCACCA TGCTGCAGAT 420 GTTGGCACTG CTGGGCTATG GCCTCTTTGG GCATTGCATT GTCCTGTTCA TCACCTATAA 480 TATCCACCTC CACGCCCTCT TCTACCTCTT CTGGCTGTTG GTGGGTGGAC TGTCCACACT 540 GCGCATGGTA GCAGTGTTGG TGTCTCGGAC CGTGGGCCCC ACACAGCGGC TGCTCCTCTG 600 TGGCACCCTG GCTGCCCTAC ACATGCTCTT CCTGCTCTAT CTGCATTTTG CCTACCACAA 660 AGTGGTAGAG GGGATCCTGG ACACACTGGA GGGCCCCAAC ATCCCGCCCA TCCAGAGGGT 720 CCCCAGAGAC ATCCCTGCCA TGCTCCCTGC TGCTCGGCTT CCCACCACCG TCCTCAACGC 780 CACAGCCAAA GCTGTTGCGG TGACCCTGCA GTCACACTGA CCCCACCTGA AATTCTTGGC 840 CAGTCCTCTT TCCCGCAGCT GCAGAGAGGA GGAAGACTAT TAAAGGACAG TCCTGATGAC 900 ATGTTTCGTA GATGGGGTTT GCAGCTGCCA CTGAGCTGTA GCTGCGTAAG TACCTCCTTG 960 ATGCCTGTCG GCACTTCTGA AAGGCACAAG GCCAAGAACT CCTGGCCAGG ACTGCAAGGC 1020 TCTGCAGCCA ATGCAGAAAA TGGGTCAGCT CCTTTGAGAA CCCCTCCCCA CCTACCCCTT 1080 CCTTCCTCTT TATCTCTCCC ACATTGTCTT GCTAAATATA GACTTGGTAA TTAAAATGTT 1140 GATTGAAGTC TGGAAAAAAA AAAAAAAAAA AATTCCTGCG GCCGC 1185 (2) INFORMATION FOR SEQ ID NO: 9: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1226 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 9: GAATTCGGCA CGAGGCAAGC CACCATCTTC CTTCGGCCTG CACCCCTTTA AAGGCACCCA 60 GACCCCTCTG GAAAAAGATG AACTGAAGCC CTTTGACATC CTCCAGCCTA AGGAGTACTT 120 CCAGCTCAGC CGCCACACGG TCATTAAGAT GGGAAGTGAG AACGAGGCCC TGGATCTCTC 180 CATGAAGTCA GTGCCCTGGC TCAAGGCTGG TGAAGTCAGT CCCCCAATCT TCCAGGAAGA 240 TGCAGCCCTA GACCTGTCAG TGGCAGCCCA CCGGAAATCC GAGCCTCCCC CTGAGACACT 300 GTATGACAGT GGTGCATCAG TGGACAGCTC AGGTCACACA GTGATGGAGA AACTTCCCAG 360 TGGCATGGAA ATTTCTTTTG CCCCTGCCAC GTCCCATGAG GCCCCAGCCA TGATGGATAG 420 TCACATCAGC AGCAGTGATG CTGCTACCGA GATGCTCAGC CAGCCCAACC ACCCCAGCGG 480 CGAAGTCAAG GCTGAAAATA ACATTGAGAT GGTGGGCGAG TCCCAGGCGG CCAAGGTCAT 540 TGTCTCTGTC GAAGATGCTG TGCCTACCAT ATTCTGTGGC AAGATCAAAG GCCTCTCAGG 600 GGTGTCCACC AAAAACTTCT CCTTCAAAAG AGAAGACTCC GTGCTTCAGG GCTATGACAT 660 CAACAGCCAA GGGGAAGAGT CCATGGGAAA TGCAGAGCCC CTTAGGAAAC CCATCAAAAA 720 CCGGAGCATA AAGTTAAAGA AAGTGAACTC CCAGGAAGTA CACATGCTCC CAATCAAAAA 780 ACAACGGCTG GCCACCTTTT TTCCAAGAAA GTAAATAACG GCTTTTTAAA ATTTGTATGA 840 TTATAATATG GGGAAAGGTG CATTGGTTTT ATAAAAAGGC ATTTAAAACA AATTATCTTT 900 GTTAATTATT TTGGGGAGTA GTTGGGAAAT GGAAAGGTGA ATTGGCTCTA GAGGCCCTGT 960 ATGCTAGTAT CATTTTCTTT TTTAATTTTT GACTTTTCAC AAATGAGTAA ATAAGAGCAA 1020 CCTATTTTTC AAGCAGATTG CACATTTTTT GCAGCTTTAA TGGAATATTG GGTGAATTAG 1080 AGGGGTAAAA AAAGCTATTT TCATTGCCAC AAAGTGCTTT GATGATGTAA TACCTAATAA 1140 AGGGTAGGAT GAATATTTCA CAATAAATGT TTGTTTGCAC TAAAAAAAAA AAAAAAAAAA 1200 AAAAAAAAAA AAATTCCTGC GGCCGC 1226 (2) INFORMATION FOR SEQ ID NO: 10: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1049 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 10: GAATTCGGCA CGAGGGCGCC ATGGTGAAGG TGACGTTCAA CTCCGCTCTG GCCCAGAAGG 60 AGGCCAAGAA GGACGAGCCC AAGAGCGGCG AGGAGGCGCT CATCATCCCC CCCGACGCCG 120 TCGCGGTGGA CTGCAAGGAC CCAGATGATG TGGTACCAGT TGGCCAAAGA AGAGCCTGGT 180 GTTGGTGCAT GTGCTTTGGA CTAGCATTTA TGCTTGCAGG TGTTATTCTA GGAGGAGCAT 240 ACTTGTACAA ATATTTTGCA CTTCAACCAG ATGACGTGTA CTACTGTGGA ATAAAGTACA 300 TCAAAGATGA TGTCATCTTA AATGAGCCCT CTGCAGATGC CCCAGCTGCT CTCTACCAGA 360 CAATTGAAGA AAATATTAAA ATCTTTGAAG AAGAAGAAGT TGAATTTATC AGTGTGCCTG 420 TCCCAGAGTT TGCAGATAGT GATCCTGCCA ACATTGTTCA TGACTTTAAC AAGAAACTTA 480 CAGCCTATTT AGATCTTAAC CTGGATAAGT GCTATGTGAT CCCTCTGAAC ACTTCCATTG 540 TTATGCCACC CAGAAACCTA CTGGAGTTAC TTATTAACAT CAAGGCTGGA ACCTATTTGC 600 CTCAGTCCTA TCTGATTCAT GAGCACATGG TTATTACTGA TCGCATTGAA AACATTGATC 660 ACCTGGGTTT CTTTATTTAT CGACTGTGTC ATGACAAGGA AACTTACAAA CTGCAACGCA 720 GAGAAACTAT TAAAGGTATT CAGAAACGTG AAGCCAGCAA TTGTTTCGCA ATTCGGCATT 780 TTGAAAACAA ATTTGCCGTG GAAACTTTAA TTTGTTCTTG AACAGTCAAG AAAAACATTA 840 TTGAGGAAAA TTAATATCAC AGCATAACCC CACCCTTTAC ATTTTGTTGC AGTTGATTAT 900 TTTTTAAAGT CTTCTTTCAT GTAAGTAGCA AACAGGGCTT TACTATCTTT TCATCTCATT 960 AATTCAATTA AAACCATTAC CTTAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA 1020 AAAAAAAAAA AAAAAATTCC TGCGGCCGC 1049 (2) INFORMATION FOR SEQ ID NO: 11: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1142 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 11: GAATTCGGCA CGAGGGGAGA ATACTTTTTG CGATGCCTAC TGGAGACTTT GATTCGAAGC 60 CCAGTTGGGC CGACCAGGTG GAGGAGGAGG GGGAGGACGA CAAATGTGTC ACCAGCGAGC 120 TCCTCAAGGG GATCCCTCTG GCCACAGGTG ACACCAGCCC AGAGCCAGAG CTACTGCCGG 180 GAGCTCCACT GCCGCCTCCC AAGGAGGTCA TCAACGGAAA CATAAAGACA GTGACAGAGT 240 ACAAGATAGA TGAGGATGGC AAGAAGTTCA AGATTGTCCG CACCTTCAGG ATTGAGACCC 300 GGAAGGCTTC AAAGGCTGTC GCAAGGAGGA AGAACTGGAA GAAGTTCGGG AACTCAGAGT 360 TTGACCCCCC CGGACCCAAT GTGGCCACCA CCACTGTCAG TGACGATGTC TCTATGACGT 420 TCATCACCAG CAAAGAGGAC CTGAACTGCC AGGAGGAGGA GGACCCTATG AACAAATTCA 480 AGGGCCAGAA GATCGTGTCC TGCCGCATCT GCAAGGGCGA CCACTGGACC ACCCGCTGCC 540 CCTACAAGGA TACGCTGGGG CCCATGCAGA AGGAGCTGGC CGAGCAGCTG GGCCTGTCTA 600 CTGGCGAGAA GGAGAAGCTG CCGGGAGAGC TAGAGCCGGT GCAGGCCACG CAGAACAAGA 660 CAGGGAAGTA TGTGCCGCCG AGCCTGCGCG ACGGGGCCAG CCGCCGCGGG GAGTCCATGC 720 AGCCCAACCG CAGAGCCGAC GACAACGCCA CCATCCGTGT CACCAACTTG CGCAGAGGAC 780 ACGCGTGAGA CCGACCTGCA GGAGCTCTTC CGGCCTTTCG GCTCCATCTC CCGCATCTAC 840 CTGGCTAAGG ACAAGACCAC TGGCCAATCC AAGGGCTTTG CCTTCATCAG CTTCCACCGC 900 CGCGAGGATG CTGCGCGTGC CATTGCCGGG GTGTCCGGCT TTGGCTACGA CCACCTCATC 960 CTCAACGTCG AGTGGGCCAA GCCGTCCACC AACTAAGCCA GCTGCCACTG TGTACTCGGT 1020 CCGGGACCCT TGGCGACAGA AGACAGCCTC CGAGAGCGCG GGCTCCAAGG GCAATAAAGC 1080 AGCTCCACTC TCAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAT TCCTGCGGCC 1140 GC 1142 (2) INFORMATION FOR SEQ ID NO: 12: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1696 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 12: GAATTCGGCA CGAGGGAAAC ATGGCGGTAG GCTGGGACCA TAACACAAGC ATGACTATAT 60 GAAGGAAGAG GAAGGTTTTC CTGAAGATGA GGCGACTGAA TCGGAAAAAA ACTTTAAGTT 120 TGGTAAAAGA GTTGGATGCC TTTCCGAAGG TTCCTGAGAG CTATGTAGAG ACTTCAGCCA 180 GTGGAGGTAC AGTTTCTCTA ATAGCATTTA CAACTATGGC TTTATTAACC ATAATGGAAT 240 TCTCAGTATA TCAAGATACA TGGATGAAGT ATGAATACGA AGTAGACAAG GATTTTTCTA 300 GCAAATTAAG AATTAATATA GATATTACTG TTGCCATGAA GTGTCAATAT GTTGGAGCGG 360 ATGTATTGGA TTTAGCAGAA ACAATGGTTG CATCTGCAGA TGGTTTAGTT TATGAACCAA 420 CAGTATTTGA TCTTTCACCA CAGCAGAAAG AGTGGCAGAG GATGCTGCAG CTGATTCAGA 480 GTAGGCTACA AGAAGAGCAT TCACTTCAAG ATGTGATATT TAAAAGTGCT TTTAAAAGTA 540 CATCAACAGC TCTTCCACCA AGAGAAGATG ATTCATCACA GTCTCCAAAT GCATGCAGAA 600 TTCATGGCCA TCTATATGTC AATAAAGTAG CAGGGAATTT TCACATAACA GTGGGCAAGG 660 CAATTCCACA TCCTCGTGGT CATGCACATT TGGCAGCACT TGTCAACCAT GAATCTTACA 720 ATTTTTCTCA TAGAATAGAT CATTTGTCTT TTGGAGAGCT TGTTCCAGCA ATTATTAATC 780 CTTTAGATGG AACTGAAAAA ATTGCTATAG ATCACAACCA GATGTTCCAA TATTTTATTA 840 CAGTTGTGCC AACAAAACTA CATACATATA AAATATCAGC AGACACCCAT CAGTTTTCTG 900 TGACAGAAAG GGAACGTATC ATTAACCATG CTGCAGGCAG CCATGGAGTC TCTGGGATAT 960 TTATGAAATA TGATCTCAGT TCTCTTATGG TGACAGTTAC TGAGGAGCAC ATGCCATTCT 1020 GGCAGTTTTT TGTAAGACTC TGTGGTATTG TTGGAGGAAT CTTTTCAACA ACAGGCATGT 1080 TACATGGAAT TGGAAAATTT ATAGTTGAAA TAATTTGCTG TCGTTTCAGA CTTGGATCCT 1140 ATAAACCTGT CAATTCTGTT CCTTTTGAGG ATGGCCACAC AGACAACCAC TTACCTCTTT 1200 TAGAAAATAA TACACATTAA CACCTCCCGA TTGAAGGAGA AAAACTTTTT GCCTGAGACA 1260 TAAAACCTTT TTTTAATAAT AAAATATTGT GCAATATATT CAAAGAAAAG AAAACACAAA 1320 TAAGCAGAAA ACATACTTAT TTTAAAAAAG AAAAAAAAGG ATAAAAAAAC CCAAACTGAA 1380 ATTCTATATA CGTTGTGTCT GTTACAAATG TCGTAGAAGA AATCATGCAG CTAAACGATG 1440 AAGAAGCCCA ACTGGAGTGT TGCTTTGAAG ATGACGCCTT CTTATATTTT CATAGCAAAT 1500 GGGTGGTATC AAAATCAGAC ATTGCTTCTT GCTGATAAAA AGCCTGAAGG AAATAAGTGA 1560 AACTACATCT ATGGGAAAAA AAAAAACATT GAGAAGTGCA AATGTTCGCA TCCTTTTGTT 1620 TTTAAAAGAT ATGATGTCAG AATAAAATGT GGAAAACATA CGGAAAAAAA AAAAAAAAAA 1680 AAATTCCTGC GGCCGC 1696 (2) INFORMATION FOR SEQ ID NO: 13: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1100 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 13: GAATTCGGCA CGAGGCGGCA CGAGGCGGCA CGAGGGTGGC ATATCACGGC CATGGGGTCT 60 CAGCATTCCG CTGCTGCTCG CCCCTCCTCC TGCAGGCGAA AGCAAGAAGA TGACAGGGAC 120 GGTTTGCTGG CTGAACGAGA GCAGGAAGAA GCCATTGCTC AGTTCCCATA TGTGGAATTC 180 ACCGGGAGAG ATAGCATCAC CTGTCTCACG TGCCAGGGGA CAGGCTACAT TCCAACAGAG 240 CAAGTAAATG AGTTGGTGGC TTTGATCCCA CACAGTGATC AGAGATTGCG CCCTCAGCGA 300 ACTAAGCAAT ATGTCCTCCT GTCCATCCTG CTTTGTCTCC TGGCATCTGG TTTGGTGGTT 360 TTCTTCCTGT TTCCGCATTC AGTCCTTGTG GATGATGACG GCATCAAAGT GGTGAAAGTC 420 ACATTTAATA AGCAAGACTC CCTTGTAATT CTCACCATCA TGGCCACCCT GAAAATCAGG 480 AACTCCAACT TCTACACGGT GGCAGTGACC AGCCTGTCCA GCCAGATTCA GTACATGAAC 540 ACAGTGGTCA GTACATATGT GACTACTAAC GTCTCCCTTA TTCCACCTCG GAGTGAGCAA 600 CTGGTGAATT TTACCGGGAA GGCCGAGATG GGAGGACCGT TTTCCTATGT GTACTTCTTC 660 TGCACGGTAC CTGAGATCCT GGTGCACAAC ATAGTGATCT TCATGCGAAC TTCAGTGAAG 720 ATTTCATACA TTGGCCTCAT GACCCAGAGC TCCTTGGAGA CACATCACTA TGTGGATTGT 780 GGAGGAAATT CCACAGCTAT TTAACAACTG CTATTGGTTC TTCCACACAG CGCCTGTAGA 840 AGAGAGCACA GCATATGTTC CCAAGGCCTG AGTTCTGGAC CTACCCCCAC GTGGTGTAAG 900 CAGAGGAGGA ATTGGTTCAC TTAACTCCCA GCAAACATCC TCCTGCCACT TAGGAGGAAA 960 CACCTCCCTA TGGTACCATT TATGTTTCTC AGAACCAGCA GAATCAGTGC CTAGCCTGTG 1020 CCCAGCAAAT AGTTGGCACT CAATAAAGAT TTGCAGAATT TAAAAAAAAA AAAAAAAAAA 1080 AAAAAAATTC CTGCGGCCGC 1100 (2) INFORMATION FOR SEQ ID NO: 14: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1588 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 14: GAATTCGGCA CGAGGGTACC TGCTTTTCTA TTGCCTCTTT GAAACAATGG TCACGTGTTT 60 CCATGTTCCC TACTCGGCTC TCACCATGTT CATCAGCACC GAGCAGACTG AGCGGGATTC 120 TGCCACCGCC TATCGGATGA CTGTGGAAGT GCTGGGCACA GTGCTGGGCA CGGCGATCCA 180 GGGACAAATC GTGGGCCAAG CAGACACGCC TTGTTTCCAG GACCTCAATA GCTCTACAGT 240 AGCTTCACAA AGTGCCAACC ATACACATGG CACCACCTCA CACAGGGAAA CGCAAAAGGC 300 ATACCTGCTG GCAGCGGGGG TCATTGTCTG TATCTATATA ATCTGTGCTG TCATCCTGAT 360 CCTGGGCGTG CGGGAGCAGA GAGAACCCTA TGAAGCCCAG CAGTCTGAGC CAATCGCCTA 420 CTTCCGGGGC CTACGGCTGG TCATGAGCCA CGGCCCATAC ATCAAACTTA TTACTGGCTT 480 CCTCTTCACC TCCTTGGCTT TCATGCTGGT GGAGGGGAAC TTTGTCTTGT TTTGCACCTA 540 CACCTTGGGC TTCCGCAATG AATTCCAGAA TCTACTCCTG GCCATCATGC TCTCGGCCAC 600 TTTAACCATT CCCATCTGGC AGTGGTTCTT GACCCGGTTT GGCAAGAAGA CAGCTGTATA 660 TGTTGGGATC TCATCAGCAG TGCCATTTCT CATCTTGGTG GCCCTCATGG AGAGTAACCT 720 CATCATTACA TATGCGGTAG CTGTGGCAGC TGGCATCAGT GTGGCAGCTG CCTTCTTACT 780 ACCCTGGTCC ATGCTGCCTG ATGTCATTGA CGACTTCCAT CTGAAGCAGC CCCACTTCCA 840 TGGAACCGAG CCCATCTTCT TCTCCTTCTA TGTCTTCTTC ACCAAGTTTG CCTCTGGAGT 900 GTCACTGGGC ATTTCTACCC TCAGTCTGGA CTTTGCAGGG TACCAGACCC GTGGCTGCTC 960 GCAGCCGGAA CGTGTCAAGT TTACACTGAA CATGCTCGTG ACCATGGCTC CCATAGTTCT 1020 CATCCTGCTG GGCCTGCTGC TCTTCAAAAT GTACCCCATT GATGAGGAGA GGCGGCGGCA 1080 GAATAAGAAG GCCCTGCAGG CACTGAGGGA CGAGGCCAGC AGCTCTGGCT GCTCAGAAAC 1140 AGACTCCACA GAGCTGGCTA GCATCCTCTA GGGCCCGCCA CGTTGCCCGA AGCCACCATG 1200 CAGAAGGCCA CAGAAGGGAT CAGGACCTGT CTGCCGGCTT GCTGAGCAGC TGGACTGCAG 1260 GTGCTAGGAA GGGAACTGAA GACTCAAGGA GGTGGCCCAG GACACTTGCT GTGCTCACTG 1320 TGGGGCCGGC TGCTCTGTGG CCTCCTGCCT CCCCTCTGCC TGCCTGTGGG GCCAAGCCCT 1380 GGGGCTGCCA CTGTGAATAT GCCAAGGACT GATCGGGCCT AGCCCGGAAC ACTAATGTAG 1440 AAACCTTTTT TTTACAGAGC CTAATTAATA ACTTAATGAC TGTGTACATA GCAATGTGTG 1500 TGTATGTATA TGTCTGTGAG CTATTAATGT TATTAATTTT CATAAAAGCT GGAAAGCAAA 1560 AAAAAAAAAA AAAAATTCCT GCGGCCGC 1588 (2) INFORMATION FOR SEQ ID NO: 15: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1535 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 15: GAATTCGGCA CGAGGCGGAA GTCCCGTCTC ACGGTTGCCC TGGCAGCGCG CGAGGCTGGT 60 GAGTCGGCAG CCCTGTGGCA GCCGGCGGGC TGGTTTCCAT GGTTGCACGA TTAGGAACCA 120 CCAGCTGCTG CATCCCATGG CCAGGGGTGG CGTCCAGGTG GCAGAGCAGC TAGGAACGCA 180 AGGCCTGAAC CTGGGGCCAG ACACCCTGCT CTCCCGGCCA TGGTCAACGA CCCTCCAGTA 240 CCTGCCTTAC TGTGGGCCCA GGAGGTGGGC CAAGTCTTGG CAGGCCGTGC CCGCAGGCTG 300 CTGCTGCAGT TTGGGGTGCT CTTCTGCACC ATCCTCCTTT TGCTCTGGGT GTCTGTCTTC 360 CTCTATGGCT CCTTCTACTA TTCCTATATG CCGACAGTCA GCCACCTCAG CCCTGTGCAT 420 TTCTACTACA GGACCGACTG TGATTCCTCC ACCACCTCAC TCTGCTCCTT CCCTGTTGCC 480 AATGTCTCGC TGACTAAGGG TGGACGTGAT CGGGTGCTGA TGTATGGACA GCCGTATCGT 540 GTTACCTTAG AGCTTGAGCT GCCAGAGTCC CCTGTGAATC AAGATTTGGG CATGTTCTTG 600 GTCACCATTT CCTGCTACAC CAGAGGTGGC CGAATCATCT CCACTTCTTC GCGTTCGGTG 660 ATGCTGCATT ACCGCTCAGA CCTGCTCCAG ATGCTGGACA CACTGGTCTT CTCTAGCCTC 720 CTGCTATTTG GCTTTGCAGA GCAGAAGCAG CTGCTGGAGG TGGAACTCTA CGCAGACTAT 780 AGAGAGAACT CGTACGTGCC GACCACTGGA GCGATCATTG AGATCCACAG CAAGCGCATC 840 CAGCTGTATG GAGCCTACCT CCGCATCCAC GCGCACTTCA CTGGGCTCAG ATACCTGCTA 900 TACAACTTCC CGATGACCTG CGCCTTCATA GGTGTTGCCA GCAACTTCAC CTTCCTCAGC 960 GTCATCGTGC TCTTCAGCTA CATGCAGTGG GTGTGGGGGG GCATCTGGCC CCGACACCGC 1020 TTCTCTTTGC AGGTTAACAT CCGAAAAAGA GACAATTCCC GGAAGGAAGT CCAACGAAGG 1080 ATCTCTGCTC ATCAGCCAGG GCCTGAAGGC CAGGAGGAGT CAACTCCGCA ATCAGATGTT 1140 ACAGAGGATG GTGAGAGCCC TGAAGATCCC TCAGGGACAG AGGTCAGCTG TCCGAGGAGG 1200 AGAAACCAGA TCAGCAGCCC CTGAGCGGAG AAGAGGAGCT AGAGCCTGAG GCCAGTGATG 1260 GTTCAGGCTC CTGGGAAGAT GCAGCTTTGC TGACGGAGGC CAACCTGCCT GCTCCTGCTC 1320 CTGCTTCTGC TTCTGCCCCT GTCCTAGAGA CTCTGGGCAG CTCTGAACCT GCTGGGGGTG 1380 CTCTCCGACA GCGCCCCACC TGCTCTAGTT CCTGAAGAAA AGGGGCAGAC TCCTCACATT 1440 CCAGCACTTT CCCACCTGAC TCCTCTCCCC TCGTTTTTCC TTCAATAAAC TATTTTGTGT 1500 CAAAAAAAAA AAAAAAAAAA AATTCCTGCG GCCGC 1535 (2) INFORMATION FOR SEQ ID NO: 16: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1322 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 16: GAATTCGGCA CGAGGGCGGG CGCTACGGGC TTGACTCCCC CAAGGCCGAG GTCCGCGGCC 60 AGGTGCTGGC GCCGCTGCCC CTCCACGGAG TTGCTGATCA TCTGGGCTGT GATCCACAAA 120 CCCGGTTCTT TGTCCCTCCT AATATCAAAC AGTGGATTGC CTTGCTGCAG AGGGGAAACT 180 GCACGTTTAA AGAGAAAATA TCACGGGCCG CTTTCCACAA TGCAGTTGCT GTAGTCATCT 240 ACAATAATAA ATCCAAAGAG GAGCCAGTTA CCATGACTCA TCCAGGCACT GGAGATATTA 300 TTGCTGTCAT GATAACAGAA TTGAGGGGTA AGGATATTTT GAGTTATCTG GAGAAAAACA 360 TCTCTGTACA AATGACAATA GCTGTTGGAA CTCGAATGCC ACCGAAGAAC TTCAGCCGTG 420 GCTCTCTAGT CTTCGTGTCA ATATCCTTTA TTGTTTTGAT GATTATTTCT TCAGCATGGC 480 TCATATTCTA CTTCATTCAA AAGATCAGGT ACACAAATGC ACGCGACAGG AACCAGCGTC 540 GTCTCGGAGA TGCAGCCAAG AAAGCCATCA GTAAATTGAC AACCAGGACA GTAAAGAAGG 600 GTGACAAGGA AACTGACCCA GACTTTGATC ATTGTGCAGT CTGCATAGAG AGCTATAAGC 660 AGAATGATGT CGTCCGAATT CTCCCCTGCA AGCATGTTTT CCACAAATCC TGCGTGGATC 720 CCTGGCTTAG TGAACATTGT ACCTGTCCTA TGTGCAAACT TAATATATTG AAGGCCCTGG 780 GAATTGTGCC GAATTTGCCA TGTACTGATA ACGTAGCATT CGATATGGAA AGGCTCACCA 840 GAACCCAAGC TGTTAACCGA AGATCAGCCC TCGGCGACCT CGCCGGCGAC AACTCCCTTG 900 GCCTTGAGCC ACTTCGAACT TCGGGGATCT CACCTCTTCC TCAGGATGGG GAGCTCACTC 960 CGAGAACAGG AGAAATCAAC ATTGCAGTAA CAAAAGAATG GTTTATTATT GCCAGTTTTG 1020 GCCTCCTCAG TGCCCTCACA CTCTGCTACA TGATCATCAG AGCCACAGCT AGCTTGAATG 1080 CTAATGAGGT AGAATGGTTT TGAAGAAGAA AAAACCTGCT TTCTGACTGA TTTTGCCTTG 1140 AAGGAAAAAA GAACCTATTT TTGTGCATCA TTTACCAATC ATGCCACACA AGCATTTATT 1200 TTTAGTACAT TTTATTTTTT CATAAAATTG CTAATGCCAA AGCTTTGTAT TAAAAGAAAT 1260 AAATAATAAA ATAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAT TCCTGCGGCC 1320 GC 1322 (2) INFORMATION FOR SEQ ID NO: 17: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1711 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 17: GAATTCGGCA CGAGGCCCTC CCGCGCTCCC GGGGCGCGCG GGCCGCGCCC CCGACGCCCT 60 ACATATACTC AGGTGCGCCC CACCTGTCCG CCCGCACCTG CTGGCTCACC TCCGAGCCAC 120 CTCTGCTGCG CACCGCAGCC TCGGACCTAC AGCCCAGGAT ACTTTGGGAC TTGCCGGCGC 180 TCAGAAACGC GCCCAGACGG CCCCTCCACC TTTTGTTTGC CTAGGGTCGC CGAGAGCGCC 240 CGGAGGGAAC CGCCTGGCCT TCGGGGACCA CCAATTTTGT CTGGAACCAC CCTCCCGGCG 300 TATCCTACTC CCTGTGCCGC GAGGCCATCG CTTCACTGGA GGGGTCGATT TGTGTGTAGT 360 TTGGTGACAA GATTTGCATT CACCTGGCCC AAACCCTTTT TGTCTCTTTG GGTGACCGGA 420 AAACTCCACC TCAAGTTTTC TTTTGTGGGG CTGCCCCCCA AGTGTCGTTT GTTTTACTGT 480 AGGGTCTCCC GCCCGGCGCC CCCAGTGTTT TCTGAGGGCG GAAATGGCCA ATTCGGGCCT 540 GCAGTTGCTG GGCTTCTCCA TGGCCCTGCT GGGCTGGGTG GGTCTGGTGG CCTGCACCGC 600 CATCCCGCAG TGGCAGATGA GCTCCTATGC GGGTGACAAC ATCATCACGG CCCAGGCCAT 660 GTACAAGGGG CTGTGGATGG ACTGCGTCAC GCAGAGCACG GGGATGATGA GCTGCAAAAT 720 GTACGACTCG GTGCTCGCCC TGTCCGCGGC CTTGCAGGCC ACTCGAGCCC TAATGGTGGT 780 CTCCCTGGTG CTGGGCTTCC TGGCCATGTT TGTGGCCACG ATGGGCATGA AGTGCACGCG 840 CTGTGGGGGA GACGACAAAG TGAAGAAGGC CCGTATAGCC ATGGGTGGAG GCATAATTTT 900 CATCGTGGCA GGTCTTGCCG CCTTGGTAGC TTGCTCCTGG TATGGCCATC AGATTGTCAC 960 AGACTTTTAT AACCCTTTGA TCCCTACCAA CATTAAGTAT GAGTTTGGCC CTGCCATCTT 1020 TATTGGCTGG GCAGGGTCTG CCCTAGTCAT CCTGGGAGGT GCACTGCTCT CCTGTTCCTG 1080 TCCTGGGAAT GAGAGCAAGG CTGGGTACCG TGCACCCCGC TCTTACCCTA AGTCCAACTC 1140 TTCCAAGGAG TATGTGTGAC CTGGGATCTC CTTGCCCCAG CCTGACAGGC TATGGGAGTG 1200 TCTAGATGCC TGAAAGGGCC TGGGGCTGAG CTCAGCCTGT GGGCAGGGTG CCGGACAAAG 1260 GCCTCCTGGT CACTCTGTCC CTGCACTCCA TGTATAGTCC TCTTGGGTTG GGGGTGGGGG 1320 GGTGCCGTTG GTGGGAGAGA CAAAAAGAGG GAGAGTGTGC TTTTTGTACA GTAATAAAAA 1380 ATAAGTATTG GGAAGCAGGC TTTTTTCCCT TCAGGGCCTC TGCTTTCCTC CCGTCCAGAT 1440 CCTTGCAGGG AGCTTGGAAC CTTAGTGCAC CTACTTCAGT TCAGAACACT TAGCACCCCA 1500 CTGACTCCAC TGACAATTGA CTAAAAGATG CAGGTGCTCG TATCTCGACA TTCATTCCCA 1560 CCCCCCTCTT ATTTAAATAG CTACCAAAGT ACTTCTTTTT TAATAAAAAA ATAAAGATTT 1620 TTATTAGGTA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA AAAAAAAAAA 1680 AAAAAAAAAA AAAAAAAATT CCTGCGGCCG C 1711 (2) INFORMATION FOR SEQ ID NO: 18: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1553 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 18: GAATTCGGCA CGAGGGCAGG TCCAGAGTAA AGTCACTGAA GAGTGGAAGC GAGGAAGGAA 60 CAGGATGATT AGACCTCAGC TGCGGACCGC GGGGCTGGGA CGATGCCTCC TGCCGGGGCT 120 GCTGCTGCTC CTGGTGCCCG TCCTCTGGGC CGGGGCTGAA AAGCTACATA CCCAGCCCTC 180 CTGCCCCGCG GTCTGCCAGC CCACGCGCTG CCCCGCGCTG CCCACCTGCG CGCTGGGGAC 240 CACGCCGGTG TTCGACCTGT GCCGCTGTTG CCGCGTCTGC CCCGCGGCCG AGCGTGAAGT 300 CTGCGGCGGG GCGCAGGGCC AACCGTGCGC CCCGGGGCTG CAGTGCCTCC AGCCGCTGCG 360 CCCCGGGTTC CCCAGCACCT GCGGTTGCCC GACGCTGGGA GGGGCCGTGT GCGGCAGCGA 420 CAGGCGCACC TACCCCAGCA TGTGCGCGCT CCGGGCCGAA AACCGCGCCG CGCGCCGCCT 480 GGGCAAGGTC CCGGCCGTGC CTGTGCAGTG GGGGAACTGC GGGGATACAG GGACCAGAAG 540 CGCAGGCCCG CTCAGGAGGA ATTACAACTT CATCGCCGCG GTGGTGGAGA AGGTGGCGCC 600 ATCGGTGGTT CACGTGCAGC TGTGGGGCAG GTTACTTCAC GGCAGCAGGC TTGTTCCTGT 660 GTACAGTGGC TCTGGGTTCA TAGTGTCTGA GGACGGGCTC ATTATTACCA ATGCCCATGT 720 TGTCAGGAAC CAGCAGTGGA TTGAGGTGGT GCTCCAGAAT GGGGCCCGTT ATGAAGCTGT 780 TGTCAAGGAT ATTGACCTTA AATTGGATCT TGCGGTGATT AAGATTGAAT CAAATGCTGA 840 ACTTCCTGTA CTGATGCTGG GAAGATCATC TGACCTTCGG GCTGGAGAGT TTGTGGTGGC 900 TTTGGGCAGC CCATTTTCTC TGCAGAACAC AGCTACTGCA GGAATTGTCA GCACCAAACA 960 GCGAGGGGGC AAAGAACTGG GGATGAAGGA TTCAGATATG GACTACGTCC AGATTGATGC 1020 CACAATTAAC TATGGGAATT CTGGTGGTCC TCTGGTGAAC TTGGATGGTG ATGTGATTGG 1080 CGTCAATTCA TTGAGGGTGA CTGATGGAAT CTCCTTTGCA ATTCCTTCAG ATCGAGTTAG 1140 GCAGTTCTTG GCAGAATACC ATGAGCACCA GATGAAAGGA AAGGCGTTTT CAAATAAGAA 1200 ATATCTGGGT CTGCAAATGC TGTCCCTCAC TGTGCCCCTT AGTGAAGAAT TGAAAATGCA 1260 TTATCCAGAT TTCCCTGATG TGAGTTCTGG GGTTTATGTA TGTAAAGTGG TTGAAGGAAC 1320 AGCTGCTCAA AGCTCTGGAT TGAGAGATCA CGATGTAATT GTCAACATAA ATGGGAAACC 1380 TATTACTACT ACAACTGATG TTGTTAAAGC TCTTGACAGT GATTCCCTTT CCATGGCTGT 1440 TCTTCGGGGA AAAGATAATT TGCTCCTGAC AGTCATACCT GAAACAATCA ATTAAATATC 1500 TTGTTTTAAA GTGGGATTAT CTAAAAAAAA AAAAAAAAAA TTCCTGCGGC CGC 1553 (2) INFORMATION FOR SEQ ID NO: 19: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 1596 base pairs (B) TYPE: nucleic acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: cDNA (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 19: GAATTCGGCA CGAGGGGAGC CGCTCCCGGA GCCCGGCCGT AGAGGCTGCA ATCGCAGCCG 60 GGAGCCCGCA GCCCGCGCCC CGAGCCCGCC GCCGCCCTTC GAGGGCGCCC CAGGCCGCGC 120 CATGGTGAAG GTGACGTTCA ACTCCGCTCT GGCCCAGAAG GAGGCCAAGA AGGACGAGCC 180 CGAGAGCGGC GAGGAGGCGC TCATCATCCC CCCCGACGCC GTCGCGGTGG ACTGCAAGGA 240 CCCAGATGAT GTGGTACCAG TTGGCCAAAG AAGAGCCTGG TGTTGGTGCA TGTGCTTTGG 300 ACTAGCATTT ATGCTTGCAG GTGTTATTCT AGGAGGAGCA TACTTGTACA AATATTTTGC 360 ACTTCAACCA GATGACGTGT ACTACTGTGG AATAAAGTAC ATCAAAGATG ATGTCATCTT 420 AAATGAGCCC TCTGCAGATG CCCCAGCTGC TCTCTACCAG ACAATTGAAG AAAATATTAA 480 AATCTTTGAA GAAGAAGAAG TTGAATTTAT CAGTGTGCCT GTCCCAGAGT TTGCAGATAG 540 TGATCCTGCC AACATTGTTC ATGACTTTAA CAAGAAACTT ACAGCCTATT TAGATCTTAA 600 CCTGGATAAG TGCTATGTGA TCCCTCTGAA CACTTCCATT GTTATGCCAC CCAGAAACCT 660 ACTGGAGTTA CTTATTAACA TCAAGGCTGG AACCTATTTG CCTCAGTCCT ATCTGATTCA 720 TGAGCACATG GTTATTACTG ATCGCATTGA AAACATTGAT CACCTGGGTT TCTTTATTTA 780 TCGACTGTGT CATGACAAGG AAACTTACAA ACTGCAACGC AGAGAAACTA TTAAAGGTAT 840 TCAGAAACGT GAAGCCAGCA ATTGTTTCGC AATTCGGCAT TTTGAAAACA AATTTGCCGT 900 GGAAACTTTA ATTTGTTCTT GAACAGTCAA GAAAAACATT ATTGAGGAAA ATTAATATCA 960 CAGCATAACC CCACCCTTTA CATTTTGTGC AGTGATATTT TTTAAAGTCT CTTTCATGTA 1020 AGTAGCAAAC AGGGCTTTAC TATCTTTTCA TCTCATTAAT TCAATTAAAA CCATTACCTT 1080 AAAATTTTTT TCTTTCGAAG TGTGGTGTCT TTTATATTTG AATTAGTAAC TGTATGAAGT 1140 CATAGATAAT AGTACATGTC ACCTTAGGTA GTAGGAAGAA TTACAATTTC TTTAAATCAT 1200 TTATCTGGAT TTTTATGTTT TATTAGCATT TTCAAGAAGA CGGATTATCT AGAGAATAAT 1260 CATATATATG CATACGTAAA AATGGACCAC AGTGACTTAT TTGTAGTTGT TAGTTGCCCT 1320 GCTACCTAGT TTGTTAGTGC ATTTGAGCAC ACATTTTAAT TTTCCTCTAA TTAAAATGTG 1380 CAGTATTTTC AGTGTCAAAT ATATTTAACT ATTTAGAGAA TGATTTCCAC CTTTATGTTT 1440 TAATATCCTA GGCATCTGCT GTAATAATAT TTTAGAAAAT GTTTGGAATT TAAGAAATAA 1500 CTTGTGTTAC TAATTTGTAT AACCCATATC TGTGCAATGG AATATAAATA TCACAAAGTT 1560 GTTTAAAAAA AAAAAAAAAA AAATTCCTGC GGCCGC 1596 (2) INFORMATION FOR SEQ ID NO: 20: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 400 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 20: Met Ala Trp Arg Arg Arg Glu Ala Gly Val Gly Ala Arg Gly Val Leu 1 5 10 15 Ala Leu Ala Leu Leu Ala Leu Ala Leu Cys Val Pro Gly Ala Arg Gly 20 25 30 Arg Ala Leu Glu Trp Phe Ser Ala Val Val Asn Ile Glu Tyr Val Asp 35 40 45 Pro Gln Thr Asn Leu Thr Val Trp Ser Val Ser Glu Ser Gly Arg Phe 50 55 60 Gly Asp Ser Ser Pro Lys Glu Gly Ala His Gly Leu Val Gly Val Pro 65 70 75 80 Trp Ala Pro Gly Gly Asp Leu Glu Gly Cys Ala Pro Asp Thr Arg Phe 85 90 95 Phe Val Pro Glu Pro Gly Gly Arg Gly Ala Ala Pro Trp Val Ala Leu 100 105 110 Val Ala Arg Gly Gly Cys Thr Phe Lys Asp Lys Val Leu Val Ala Ala 115 120 125 Arg Arg Asn Ala Ser Ala Val Val Leu Tyr Asn Glu Glu Arg Tyr Gly 130 135 140 Asn Ile Thr Leu Pro Met Ser His Ala Gly Thr Gly Asn Ile Val Val 145 150 155 160 Ile Met Ile Ser Tyr Pro Lys Gly Arg Glu Ile Leu Glu Leu Val Gln 165 170 175 Lys Gly Ile Pro Val Thr Met Thr Ile Gly Val Gly Thr Arg His Val 180 185 190 Gln Glu Phe Ile Ser Gly Gln Ser Val Val Phe Val Ala Ile Ala Phe 195 200 205 Ile Thr Met Met Ile Ile Ser Leu Ala Trp Leu Ile Phe Tyr Tyr Ile 210 215 220 Gln Arg Phe Leu Tyr Thr Gly Ser Gln Ile Gly Ser Gln Ser His Arg 225 230 235 240 Lys Glu Thr Lys Lys Val Ile Gly Gln Leu Leu Leu His Thr Val Lys 245 250 255 His Gly Glu Lys Gly Ile Asp Val Asp Ala Glu Asn Cys Ala Val Cys 260 265 270 Ile Glu Asn Phe Lys Val Lys Asp Ile Ile Arg Ile Leu Pro Cys Lys 275 280 285 His Ile Phe His Arg Ile Cys Ile Asp Pro Trp Leu Leu Asp His Arg 290 295 300 Thr Cys Pro Met Cys Lys Leu Asp Val Ile Lys Ala Leu Gly Tyr Trp 305 310 315 320 Gly Glu Pro Gly Asp Val Gln Glu Met Pro Ala Pro Glu Ser Pro Pro 325 330 335 Gly Arg Asp Pro Ala Ala Asn Leu Ser Leu Ala Leu Pro Asp Asp Asp 340 345 350 Gly Ser Asp Asp Ser Ser Pro Pro Ser Ala Ser Pro Ala Glu Ser Glu 355 360 365 Pro Gln Cys Asp Pro Ser Phe Lys Gly Asp Ala Gly Glu Asn Thr Ala 370 375 380 Leu Leu Glu Ala Gly Arg Ser Asp Ser Arg His Gly Gly Pro Ile Ser 385 390 395 400 (2) INFORMATION FOR SEQ ID NO: 21: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 291 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 21: Met Asp Lys Gly Ser Ala Gly His Pro Gly Gly Val Leu Val Trp Gly 1 5 10 15 Arg Ser Pro Ala Pro Thr Ala Leu Trp Gly Ala Ser Pro Trp Leu Ser 20 25 30 Pro Leu Thr Ser Ala Leu Arg Gln Pro Leu His Arg Ala Pro Leu Leu 35 40 45 Pro Gly Gln Leu Cys Trp Ser Pro Arg Pro Leu Glu Lys Asn Lys Ala 50 55 60 Met Gly Arg Pro Leu Leu Leu Pro Leu Leu Leu Leu Leu Gln Pro Pro 65 70 75 80 Ala Phe Leu Gln Pro Gly Gly Ser Thr Gly Ser Gly Pro Ser Tyr Leu 85 90 95 Tyr Gly Val Thr Gln Pro Lys His Leu Ser Ala Ser Met Gly Gly Ser 100 105 110 Val Glu Ile Pro Phe Ser Phe Tyr Tyr Pro Trp Glu Leu Ala Ile Val 115 120 125 Pro Asn Val Arg Ile Ser Trp Arg Arg Gly His Phe His Gly Gln Ser 130 135 140 Phe Tyr Ser Thr Arg Pro Pro Ser Ile His Lys Asp Tyr Val Asn Arg 145 150 155 160 Leu Phe Leu Asn Trp Thr Glu Gly Gln Glu Ser Gly Phe Leu Arg Ile 165 170 175 Ser Asn Leu Arg Lys Glu Asp Gln Ser Val Tyr Phe Cys Arg Val Glu 180 185 190 Leu Asp Thr Arg Arg Ser Gly Arg Gln Gln Leu Gln Ser Ile Lys Gly 195 200 205 Thr Lys Leu Thr Ile Thr Gln Ala Val Thr Thr Thr Thr Thr Trp Arg 210 215 220 Pro Ser Ser Thr Thr Thr Ile Ala Gly Leu Arg Val Thr Glu Ser Lys 225 230 235 240 Gly His Ser Glu Ser Trp His Leu Ser Leu Asp Thr Ala Ile Arg Val 245 250 255 Ala Leu Ala Val Ala Val Leu Lys Thr Val Ile Leu Gly Leu Leu Cys 260 265 270 Leu Leu Leu Leu Trp Trp Arg Arg Arg Lys Gly Ser Arg Ala Pro Ser 275 280 285 Ser Asp Phe 290 (2) INFORMATION FOR SEQ ID NO: 22: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 293 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 22: Met Thr Val Ser Gln Arg Phe Gln Leu Ser Asn Ser Gly Pro Asn Ser 1 5 10 15 Thr Ile Lys Met Lys Ile Ala Leu Arg Val Leu His Leu Glu Lys Arg 20 25 30 Glu Arg Pro Pro Asp His Gln His Ser Ala Gln Val Lys Arg Pro Ser 35 40 45 Val Ser Lys Glu Gly Arg Lys Thr Ser Ile Lys Ser His Met Ser Gly 50 55 60 Ser Pro Gly Pro Gly Gly Ser Asn Thr Ala Pro Ser Thr Pro Val Ile 65 70 75 80 Gly Gly Ser Asp Lys Pro Gly Met Glu Glu Lys Ala Gln Pro Pro Glu 85 90 95 Ala Gly Pro Gln Gly Leu His Asp Leu Gly Arg Ser Ser Ser Ser Leu 100 105 110 Leu Ala Ser Pro Gly His Ile Ser Val Lys Glu Pro Thr Pro Ser Ile 115 120 125 Ala Ser Asp Ile Ser Leu Pro Ile Ala Thr Gln Glu Leu Arg Gln Arg 130 135 140 Leu Arg Gln Leu Glu Asn Gly Thr Thr Leu Gly Gln Ser Pro Leu Gly 145 150 155 160 Gln Ile Gln Leu Thr Ile Arg His Ser Ser Gln Arg Asn Lys Leu Ile 165 170 175 Val Val Val His Ala Cys Arg Asn Leu Ile Ala Phe Ser Glu Asp Gly 180 185 190 Ser Asp Pro Tyr Val Arg Met Tyr Leu Leu Pro Asp Lys Arg Arg Ser 195 200 205 Gly Arg Arg Lys Thr His Val Ser Lys Lys Thr Leu Asn Pro Val Phe 210 215 220 Asp Gln Ser Phe Asp Phe Ser Val Ser Leu Pro Glu Val Gln Arg Arg 225 230 235 240 Thr Leu Asp Val Ala Val Lys Asn Ser Gly Gly Phe Leu Ser Lys Asp 245 250 255 Lys Gly Leu Leu Gly Lys Val Leu Val Ala Leu Ala Ser Glu Glu Leu 260 265 270 Ala Lys Gly Trp Thr Gln Trp Tyr Asp Leu Thr Glu Asp Gly Thr Arg 275 280 285 Pro Gln Ala Met Thr 290 (2) INFORMATION FOR SEQ ID NO: 23: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 206 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 23: Met Glu Arg Arg His Pro Val Cys Ser Gly Thr Cys Gln Pro Thr Gln 1 5 10 15 Phe Arg Cys Ser Asn Gly Cys Cys Ile Asp Ser Phe Leu Glu Cys Asp 20 25 30 Asp Thr Pro Asn Cys Pro Asp Ala Ser Asp Glu Ala Ala Cys Glu Lys 35 40 45 Tyr Thr Ser Gly Phe Asp Glu Leu Gln Arg Ile His Phe Pro Ser Asp 50 55 60 Lys Gly His Cys Val Asp Leu Pro Asp Thr Gly Leu Cys Lys Glu Ser 65 70 75 80 Ile Pro Arg Trp Tyr Tyr Asn Pro Phe Ser Glu His Cys Ala Arg Phe 85 90 95 Thr Tyr Gly Gly Cys Tyr Gly Asn Lys Asn Asn Phe Glu Glu Glu Gln 100 105 110 Gln Cys Leu Glu Ser Cys Arg Gly Ile Ser Lys Lys Asp Val Phe Gly 115 120 125 Leu Arg Arg Glu Ile Pro Ile Pro Ser Thr Gly Ser Val Glu Met Ala 130 135 140 Val Ala Val Phe Leu Val Ile Cys Ile Val Val Val Val Ala Ile Leu 145 150 155 160 Gly Tyr Cys Phe Phe Lys Asn Gln Arg Lys Asp Phe His Gly His His 165 170 175 His His Pro Pro Pro Thr Pro Ala Ser Ser Thr Val Ser Thr Thr Glu 180 185 190 Asp Thr Glu His Leu Val Tyr Asn His Thr Thr Arg Pro Leu 195 200 205 (2) INFORMATION FOR SEQ ID NO: 24: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 220 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 24: Met Ala Gly Leu Ser Arg Gly Ser Ala Arg Ala Leu Leu Ala Ala Leu 1 5 10 15 Leu Ala Ser Thr Leu Leu Ala Leu Leu Val Ser Pro Ala Arg Gly Arg 20 25 30 Gly Gly Arg Asp His Gly Asp Trp Asp Glu Ala Ser Arg Leu Pro Pro 35 40 45 Leu Pro Pro Arg Glu Asp Ala Ala Arg Val Ala Arg Phe Val Thr His 50 55 60 Val Ser Asp Trp Gly Ala Leu Ala Thr Ile Ser Thr Leu Glu Ala Val 65 70 75 80 Arg Gly Arg Pro Phe Ala Asp Val Leu Ser Leu Ser Asp Gly Pro Pro 85 90 95 Gly Ala Gly Ser Gly Val Pro Tyr Phe Tyr Leu Ser Pro Leu Gln Leu 100 105 110 Ser Val Ser Asn Leu Gln Glu Asn Pro Tyr Ala Thr Leu Thr Met Thr 115 120 125 Leu Ala Gln Thr Asn Phe Cys Lys Lys His Gly Phe Asp Pro Gln Ser 130 135 140 Pro Leu Cys Val His Ile Met Leu Ser Gly Thr Val Thr Lys Val Asn 145 150 155 160 Glu Thr Glu Met Asp Ile Ala Lys His Ser Leu Phe Ile Arg His Pro 165 170 175 Glu Met Lys Thr Trp Pro Ser Ser His Asn Trp Phe Phe Ala Lys Leu 180 185 190 Asn Ile Thr Asn Ile Trp Val Leu Asp Tyr Phe Gly Gly Pro Lys Ile 195 200 205 Val Thr Pro Glu Glu Tyr Tyr Asn Val Thr Val Gln 210 215 220 (2) INFORMATION FOR SEQ ID NO: 25: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 197 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 25: Met Asp His His Cys Pro Trp Leu Asn Asn Cys Val Gly His Tyr Asn 1 5 10 15 His Arg Tyr Phe Phe Ser Phe Cys Phe Phe Met Thr Leu Gly Cys Val 20 25 30 Tyr Cys Ser Tyr Gly Ser Trp Asp Leu Phe Arg Glu Ala Tyr Ala Ala 35 40 45 Ile Glu Lys Met Lys Gln Leu Asp Lys Asn Lys Leu Gln Ala Val Ala 50 55 60 Asn Gln Thr Tyr His Gln Thr Pro Pro Pro Thr Phe Ser Phe Arg Glu 65 70 75 80 Arg Met Thr His Lys Ser Leu Val Tyr Leu Trp Phe Leu Cys Ser Ser 85 90 95 Val Ala Leu Ala Leu Gly Ala Leu Thr Val Trp His Ala Val Leu Ile 100 105 110 Ser Arg Gly Glu Thr Ser Ile Glu Arg His Ile Asn Lys Lys Glu Arg 115 120 125 Arg Arg Leu Gln Ala Lys Gly Arg Val Phe Arg Asn Pro Tyr Asn Tyr 130 135 140 Gly Cys Leu Asp Asn Trp Lys Val Phe Leu Gly Val Asp Thr Gly Arg 145 150 155 160 His Trp Leu Thr Arg Val Leu Leu Pro Ser Thr His Leu Pro His Gly 165 170 175 Asn Gly Met Ser Trp Glu Pro Pro Pro Trp Val Thr Ala His Ser Ala 180 185 190 Ser Val Met Ala Val 195 (2) INFORMATION FOR SEQ ID NO: 26: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 451 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 26: Met Ala Pro Leu Gly Met Leu Leu Gly Leu Leu Met Ala Ala Cys Phe 1 5 10 15 Thr Phe Cys Leu Ser His Gln Asn Leu Lys Glu Phe Ala Leu Thr Asn 20 25 30 Pro Glu Lys Ser Ser Thr Lys Glu Thr Glu Arg Lys Glu Thr Lys Ala 35 40 45 Glu Glu Glu Leu Asp Ala Glu Val Leu Glu Val Phe His Pro Thr His 50 55 60 Glu Trp Gln Ala Leu Gln Pro Gly Gln Ala Val Pro Ala Gly Ser His 65 70 75 80 Val Arg Leu Asn Leu Gln Thr Gly Glu Arg Glu Ala Lys Leu Gln Tyr 85 90 95 Glu Asp Lys Phe Arg Asn Asn Leu Lys Gly Lys Arg Leu Asp Ile Asn 100 105 110 Thr Asn Thr Tyr Thr Ser Gln Asp Leu Lys Ser Ala Leu Ala Lys Phe 115 120 125 Lys Glu Gly Ala Glu Met Glu Ser Ser Lys Glu Asp Lys Ala Arg Gln 130 135 140 Ala Glu Val Lys Arg Leu Phe Arg Pro Ile Glu Glu Leu Lys Lys Asp 145 150 155 160 Phe Asp Glu Leu Asn Val Val Ile Glu Thr Asp Met Gln Ile Met Val 165 170 175 Arg Leu Ile Asn Lys Phe Asn Ser Ser Ser Ser Ser Leu Glu Glu Lys 180 185 190 Ile Ala Ala Leu Phe Asp Leu Glu Tyr Tyr Val His Gln Met Asp Asn 195 200 205 Ala Gln Asp Leu Leu Ser Phe Gly Gly Leu Gln Val Val Ile Asn Gly 210 215 220 Leu Asn Ser Thr Glu Pro Leu Val Lys Glu Tyr Ala Ala Phe Val Leu 225 230 235 240 Gly Ala Ala Phe Ser Ser Asn Pro Lys Val Gln Val Glu Ala Ile Glu 245 250 255 Gly Gly Ala Leu Gln Lys Leu Leu Val Ile Leu Ala Thr Glu Gln Pro 260 265 270 Leu Thr Ala Lys Lys Lys Val Leu Phe Ala Leu Cys Ser Leu Leu Arg 275 280 285 His Phe Pro Tyr Ala Gln Arg Gln Phe Leu Lys Leu Gly Gly Leu Gln 290 295 300 Val Leu Arg Thr Leu Val Gln Glu Lys Gly Thr Glu Val Leu Ala Val 305 310 315 320 Arg Val Val Thr Leu Leu Tyr Asp Leu Val Thr Glu Lys Met Phe Ala 325 330 335 Glu Glu Glu Ala Glu Leu Thr Gln Glu Met Ser Pro Glu Lys Leu Gln 340 345 350 Gln Tyr Arg Gln Val His Leu Leu Pro Gly Leu Trp Glu Gln Gly Trp 355 360 365 Cys Glu Ile Thr Ala His Leu Leu Ala Leu Pro Glu His Asp Ala Arg 370 375 380 Glu Lys Val Leu Gln Thr Leu Gly Val Leu Leu Thr Thr Cys Arg Asp 385 390 395 400 Arg Tyr Arg Gln Asp Pro Gln Leu Gly Arg Thr Leu Ala Ser Leu Gln 405 410 415 Ala Glu Tyr Gln Val Leu Ala Ser Leu Glu Leu Gln Asp Gly Glu Asp 420 425 430 Glu Gly Tyr Phe Gln Glu Leu Leu Gly Ser Val Asn Ser Leu Leu Lys 435 440 445 Glu Leu Arg 450 (2) INFORMATION FOR SEQ ID NO: 27: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 254 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 27: Met Trp Gln Ala Gly Lys Arg Gln Ala Ser Arg Ala Phe Ser Leu Tyr 1 5 10 15 Ala Asn Ile Asp Ile Leu Arg Pro Tyr Phe Asp Val Glu Pro Ala Gln 20 25 30 Val Arg Ser Arg Leu Leu Glu Ser Met Ile Pro Ile Lys Met Val Asn 35 40 45 Phe Pro Gln Lys Ile Ala Gly Glu Leu Tyr Gly Pro Leu Met Leu Val 50 55 60 Phe Thr Leu Val Ala Ile Leu Leu His Gly Met Lys Thr Ser Asp Thr 65 70 75 80 Ile Ile Arg Glu Gly Thr Leu Met Gly Thr Ala Ile Gly Thr Cys Phe 85 90 95 Gly Tyr Trp Leu Gly Val Ser Ser Phe Ile Tyr Phe Leu Ala Tyr Leu 100 105 110 Cys Asn Ala Gln Ile Thr Met Leu Gln Met Leu Ala Leu Leu Gly Tyr 115 120 125 Gly Leu Phe Gly His Cys Ile Val Leu Phe Ile Thr Tyr Asn Ile His 130 135 140 Leu His Ala Leu Phe Tyr Leu Phe Trp Leu Leu Val Gly Gly Leu Ser 145 150 155 160 Thr Leu Arg Met Val Ala Val Leu Val Ser Arg Thr Val Gly Pro Thr 165 170 175 Gln Arg Leu Leu Leu Cys Gly Thr Leu Ala Ala Leu His Met Leu Phe 180 185 190 Leu Leu Tyr Leu His Phe Ala Tyr His Lys Val Val Glu Gly Ile Leu 195 200 205 Asp Thr Leu Glu Gly Pro Asn Ile Pro Pro Ile Gln Arg Val Pro Arg 210 215 220 Asp Ile Pro Ala Met Leu Pro Ala Ala Arg Leu Pro Thr Thr Val Leu 225 230 235 240 Asn Ala Thr Ala Lys Ala Val Ala Val Thr Leu Gln Ser His 245 250 (2) INFORMATION FOR SEQ ID NO: 28: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 221 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 28: Met Gly Ser Glu Asn Glu Ala Leu Asp Leu Ser Met Lys Ser Val Pro 1 5 10 15 Trp Leu Lys Ala Gly Glu Val Ser Pro Pro Ile Phe Gln Glu Asp Ala 20 25 30 Ala Leu Asp Leu Ser Val Ala Ala His Arg Lys Ser Glu Pro Pro Pro 35 40 45 Glu Thr Leu Tyr Asp Ser Gly Ala Ser Val Asp Ser Ser Gly His Thr 50 55 60 Val Met Glu Lys Leu Pro Ser Gly Met Glu Ile Ser Phe Ala Pro Ala 65 70 75 80 Thr Ser His Glu Ala Pro Ala Met Met Asp Ser His Ile Ser Ser Ser 85 90 95 Asp Ala Ala Thr Glu Met Leu Ser Gln Pro Asn His Pro Ser Gly Glu 100 105 110 Val Lys Ala Glu Asn Asn Ile Glu Met Val Gly Glu Ser Gln Ala Ala 115 120 125 Lys Val Ile Val Ser Val Glu Asp Ala Val Pro Thr Ile Phe Cys Gly 130 135 140 Lys Ile Lys Gly Leu Ser Gly Val Ser Thr Lys Asn Phe Ser Phe Lys 145 150 155 160 Arg Glu Asp Ser Val Leu Gln Gly Tyr Asp Ile Asn Ser Gln Gly Glu 165 170 175 Glu Ser Met Gly Asn Ala Glu Pro Leu Arg Lys Pro Ile Lys Asn Arg 180 185 190 Ser Ile Lys Leu Lys Lys Val Asn Ser Gln Glu Val His Met Leu Pro 195 200 205 Ile Lys Lys Gln Arg Leu Ala Thr Phe Phe Pro Arg Lys 210 215 220 (2) INFORMATION FOR SEQ ID NO: 29: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 266 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 29: Met Val Lys Val Thr Phe Asn Ser Ala Leu Ala Gln Lys Glu Ala Lys 1 5 10 15 Lys Asp Glu Pro Lys Ser Gly Glu Glu Ala Leu Ile Ile Pro Pro Asp 20 25 30 Ala Val Ala Val Asp Cys Lys Asp Pro Asp Asp Val Val Pro Val Gly 35 40 45 Gln Arg Arg Ala Trp Cys Trp Cys Met Cys Phe Gly Leu Ala Phe Met 50 55 60 Leu Ala Gly Val Ile Leu Gly Gly Ala Tyr Leu Tyr Lys Tyr Phe Ala 65 70 75 80 Leu Gln Pro Asp Asp Val Tyr Tyr Cys Gly Ile Lys Tyr Ile Lys Asp 85 90 95 Asp Val Ile Leu Asn Glu Pro Ser Ala Asp Ala Pro Ala Ala Leu Tyr 100 105 110 Gln Thr Ile Glu Glu Asn Ile Lys Ile Phe Glu Glu Glu Glu Val Glu 115 120 125 Phe Ile Ser Val Pro Val Pro Glu Phe Ala Asp Ser Asp Pro Ala Asn 130 135 140 Ile Val His Asp Phe Asn Lys Lys Leu Thr Ala Tyr Leu Asp Leu Asn 145 150 155 160 Leu Asp Lys Cys Tyr Val Ile Pro Leu Asn Thr Ser Ile Val Met Pro 165 170 175 Pro Arg Asn Leu Leu Glu Leu Leu Ile Asn Ile Lys Ala Gly Thr Tyr 180 185 190 Leu Pro Gln Ser Tyr Leu Ile His Glu His Met Val Ile Thr Asp Arg 195 200 205 Ile Glu Asn Ile Asp His Leu Gly Phe Phe Ile Tyr Arg Leu Cys His 210 215 220 Asp Lys Glu Thr Tyr Lys Leu Gln Arg Arg Glu Thr Ile Lys Gly Ile 225 230 235 240 Gln Lys Arg Glu Ala Ser Asn Cys Phe Ala Ile Arg His Phe Glu Asn 245 250 255 Lys Phe Ala Val Glu Thr Leu Ile Cys Ser 260 265 (2) INFORMATION FOR SEQ ID NO: 30: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 251 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 30: Met Pro Thr Gly Asp Phe Asp Ser Lys Pro Ser Trp Ala Asp Gln Val 1 5 10 15 Glu Glu Glu Gly Glu Asp Asp Lys Cys Val Thr Ser Glu Leu Leu Lys 20 25 30 Gly Ile Pro Leu Ala Thr Gly Asp Thr Ser Pro Glu Pro Glu Leu Leu 35 40 45 Pro Gly Ala Pro Leu Pro Pro Pro Lys Glu Val Ile Asn Gly Asn Ile 50 55 60 Lys Thr Val Thr Glu Tyr Lys Ile Asp Glu Asp Gly Lys Lys Phe Lys 65 70 75 80 Ile Val Arg Thr Phe Arg Ile Glu Thr Arg Lys Ala Ser Lys Ala Val 85 90 95 Ala Arg Arg Lys Asn Trp Lys Lys Phe Gly Asn Ser Glu Phe Asp Pro 100 105 110 Pro Gly Pro Asn Val Ala Thr Thr Thr Val Ser Asp Asp Val Ser Met 115 120 125 Thr Phe Ile Thr Ser Lys Glu Asp Leu Asn Cys Gln Glu Glu Glu Asp 130 135 140 Pro Met Asn Lys Phe Lys Gly Gln Lys Ile Val Ser Cys Arg Ile Cys 145 150 155 160 Lys Gly Asp His Trp Thr Thr Arg Cys Pro Tyr Lys Asp Thr Leu Gly 165 170 175 Pro Met Gln Lys Glu Leu Ala Glu Gln Leu Gly Leu Ser Thr Gly Glu 180 185 190 Lys Glu Lys Leu Pro Gly Glu Leu Glu Pro Val Gln Ala Thr Gln Asn 195 200 205 Lys Thr Gly Lys Tyr Val Pro Pro Ser Leu Arg Asp Gly Ala Ser Arg 210 215 220 Arg Gly Glu Ser Met Gln Pro Asn Arg Arg Ala Asp Asp Asn Ala Thr 225 230 235 240 Ile Arg Val Thr Asn Leu Arg Arg Gly His Ala 245 250 (2) INFORMATION FOR SEQ ID NO: 31: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 377 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 31: Met Arg Arg Leu Asn Arg Lys Lys Thr Leu Ser Leu Val Lys Glu Leu 1 5 10 15 Asp Ala Phe Pro Lys Val Pro Glu Ser Tyr Val Glu Thr Ser Ala Ser 20 25 30 Gly Gly Thr Val Ser Leu Ile Ala Phe Thr Thr Met Ala Leu Leu Thr 35 40 45 Ile Met Glu Phe Ser Val Tyr Gln Asp Thr Trp Met Lys Tyr Glu Tyr 50 55 60 Glu Val Asp Lys Asp Phe Ser Ser Lys Leu Arg Ile Asn Ile Asp Ile 65 70 75 80 Thr Val Ala Met Lys Cys Gln Tyr Val Gly Ala Asp Val Leu Asp Leu 85 90 95 Ala Glu Thr Met Val Ala Ser Ala Asp Gly Leu Val Tyr Glu Pro Thr 100 105 110 Val Phe Asp Leu Ser Pro Gln Gln Lys Glu Trp Gln Arg Met Leu Gln 115 120 125 Leu Ile Gln Ser Arg Leu Gln Glu Glu His Ser Leu Gln Asp Val Ile 130 135 140 Phe Lys Ser Ala Phe Lys Ser Thr Ser Thr Ala Leu Pro Pro Arg Glu 145 150 155 160 Asp Asp Ser Ser Gln Ser Pro Asn Ala Cys Arg Ile His Gly His Leu 165 170 175 Tyr Val Asn Lys Val Ala Gly Asn Phe His Ile Thr Val Gly Lys Ala 180 185 190 Ile Pro His Pro Arg Gly His Ala His Leu Ala Ala Leu Val Asn His 195 200 205 Glu Ser Tyr Asn Phe Ser His Arg Ile Asp His Leu Ser Phe Gly Glu 210 215 220 Leu Val Pro Ala Ile Ile Asn Pro Leu Asp Gly Thr Glu Lys Ile Ala 225 230 235 240 Ile Asp His Asn Gln Met Phe Gln Tyr Phe Ile Thr Val Val Pro Thr 245 250 255 Lys Leu His Thr Tyr Lys Ile Ser Ala Asp Thr His Gln Phe Ser Val 260 265 270 Thr Glu Arg Glu Arg Ile Ile Asn His Ala Ala Gly Ser His Gly Val 275 280 285 Ser Gly Ile Phe Met Lys Tyr Asp Leu Ser Ser Leu Met Val Thr Val 290 295 300 Thr Glu Glu His Met Pro Phe Trp Gln Phe Phe Val Arg Leu Cys Gly 305 310 315 320 Ile Val Gly Gly Ile Phe Ser Thr Thr Gly Met Leu His Gly Ile Gly 325 330 335 Lys Phe Ile Val Glu Ile Ile Cys Cys Arg Phe Arg Leu Gly Ser Tyr 340 345 350 Lys Pro Val Asn Ser Val Pro Phe Glu Asp Gly His Thr Asp Asn His 355 360 365 Leu Pro Leu Leu Glu Asn Asn Thr His 370 375 (2) INFORMATION FOR SEQ ID NO: 32: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 250 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 32: Met Gly Ser Gln His Ser Ala Ala Ala Arg Pro Ser Ser Cys Arg Arg 1 5 10 15 Lys Gln Glu Asp Asp Arg Asp Gly Leu Leu Ala Glu Arg Glu Gln Glu 20 25 30 Glu Ala Ile Ala Gln Phe Pro Tyr Val Glu Phe Thr Gly Arg Asp Ser 35 40 45 Ile Thr Cys Leu Thr Cys Gln Gly Thr Gly Tyr Ile Pro Thr Glu Gln 50 55 60 Val Asn Glu Leu Val Ala Leu Ile Pro His Ser Asp Gln Arg Leu Arg 65 70 75 80 Pro Gln Arg Thr Lys Gln Tyr Val Leu Leu Ser Ile Leu Leu Cys Leu 85 90 95 Leu Ala Ser Gly Leu Val Val Phe Phe Leu Phe Pro His Ser Val Leu 100 105 110 Val Asp Asp Asp Gly Ile Lys Val Val Lys Val Thr Phe Asn Lys Gln 115 120 125 Asp Ser Leu Val Ile Leu Thr Ile Met Ala Thr Leu Lys Ile Arg Asn 130 135 140 Ser Asn Phe Tyr Thr Val Ala Val Thr Ser Leu Ser Ser Gln Ile Gln 145 150 155 160 Tyr Met Asn Thr Val Val Ser Thr Tyr Val Thr Thr Asn Val Ser Leu 165 170 175 Ile Pro Pro Arg Ser Glu Gln Leu Val Asn Phe Thr Gly Lys Ala Glu 180 185 190 Met Gly Gly Pro Phe Ser Tyr Val Tyr Phe Phe Cys Thr Val Pro Glu 195 200 205 Ile Leu Val His Asn Ile Val Ile Phe Met Arg Thr Ser Val Lys Ile 210 215 220 Ser Tyr Ile Gly Leu Met Thr Gln Ser Ser Leu Glu Thr His His Tyr 225 230 235 240 Val Asp Cys Gly Gly Asn Ser Thr Ala Ile 245 250 (2) INFORMATION FOR SEQ ID NO: 33: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 374 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 33: Met Val Thr Cys Phe His Val Pro Tyr Ser Ala Leu Thr Met Phe Ile 1 5 10 15 Ser Thr Glu Gln Thr Glu Arg Asp Ser Ala Thr Ala Tyr Arg Met Thr 20 25 30 Val Glu Val Leu Gly Thr Val Leu Gly Thr Ala Ile Gln Gly Gln Ile 35 40 45 Val Gly Gln Ala Asp Thr Pro Cys Phe Gln Asp Leu Asn Ser Ser Thr 50 55 60 Val Ala Ser Gln Ser Ala Asn His Thr His Gly Thr Thr Ser His Arg 65 70 75 80 Glu Thr Gln Lys Ala Tyr Leu Leu Ala Ala Gly Val Ile Val Cys Ile 85 90 95 Tyr Ile Ile Cys Ala Val Ile Leu Ile Leu Gly Val Arg Glu Gln Arg 100 105 110 Glu Pro Tyr Glu Ala Gln Gln Ser Glu Pro Ile Ala Tyr Phe Arg Gly 115 120 125 Leu Arg Leu Val Met Ser His Gly Pro Tyr Ile Lys Leu Ile Thr Gly 130 135 140 Phe Leu Phe Thr Ser Leu Ala Phe Met Leu Val Glu Gly Asn Phe Val 145 150 155 160 Leu Phe Cys Thr Tyr Thr Leu Gly Phe Arg Asn Glu Phe Gln Asn Leu 165 170 175 Leu Leu Ala Ile Met Leu Ser Ala Thr Leu Thr Ile Pro Ile Trp Gln 180 185 190 Trp Phe Leu Thr Arg Phe Gly Lys Lys Thr Ala Val Tyr Val Gly Ile 195 200 205 Ser Ser Ala Val Pro Phe Leu Ile Leu Val Ala Leu Met Glu Ser Asn 210 215 220 Leu Ile Ile Thr Tyr Ala Val Ala Val Ala Ala Gly Ile Ser Val Ala 225 230 235 240 Ala Ala Phe Leu Leu Pro Trp Ser Met Leu Pro Asp Val Ile Asp Asp 245 250 255 Phe His Leu Lys Gln Pro His Phe His Gly Thr Glu Pro Ile Phe Phe 260 265 270 Ser Phe Tyr Val Phe Phe Thr Lys Phe Ala Ser Gly Val Ser Leu Gly 275 280 285 Ile Ser Thr Leu Ser Leu Asp Phe Ala Gly Tyr Gln Thr Arg Gly Cys 290 295 300 Ser Gln Pro Glu Arg Val Lys Phe Thr Leu Asn Met Leu Val Thr Met 305 310 315 320 Ala Pro Ile Val Leu Ile Leu Leu Gly Leu Leu Leu Phe Lys Met Tyr 325 330 335 Pro Ile Asp Glu Glu Arg Arg Arg Gln Asn Lys Lys Ala Leu Gln Ala 340 345 350 Leu Arg Asp Glu Ala Ser Ser Ser Gly Cys Ser Glu Thr Asp Ser Thr 355 360 365 Glu Leu Ala Ser Ile Leu 370 (2) INFORMATION FOR SEQ ID NO: 34: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 334 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 34: Met Val Asn Asp Pro Pro Val Pro Ala Leu Leu Trp Ala Gln Glu Val 1 5 10 15 Gly Gln Val Leu Ala Gly Arg Ala Arg Arg Leu Leu Leu Gln Phe Gly 20 25 30 Val Leu Phe Cys Thr Ile Leu Leu Leu Leu Trp Val Ser Val Phe Leu 35 40 45 Tyr Gly Ser Phe Tyr Tyr Ser Tyr Met Pro Thr Val Ser His Leu Ser 50 55 60 Pro Val His Phe Tyr Tyr Arg Thr Asp Cys Asp Ser Ser Thr Thr Ser 65 70 75 80 Leu Cys Ser Phe Pro Val Ala Asn Val Ser Leu Thr Lys Gly Gly Arg 85 90 95 Asp Arg Val Leu Met Tyr Gly Gln Pro Tyr Arg Val Thr Leu Glu Leu 100 105 110 Glu Leu Pro Glu Ser Pro Val Asn Gln Asp Leu Gly Met Phe Leu Val 115 120 125 Thr Ile Ser Cys Tyr Thr Arg Gly Gly Arg Ile Ile Ser Thr Ser Ser 130 135 140 Arg Ser Val Met Leu His Tyr Arg Ser Asp Leu Leu Gln Met Leu Asp 145 150 155 160 Thr Leu Val Phe Ser Ser Leu Leu Leu Phe Gly Phe Ala Glu Gln Lys 165 170 175 Gln Leu Leu Glu Val Glu Leu Tyr Ala Asp Tyr Arg Glu Asn Ser Tyr 180 185 190 Val Pro Thr Thr Gly Ala Ile Ile Glu Ile His Ser Lys Arg Ile Gln 195 200 205 Leu Tyr Gly Ala Tyr Leu Arg Ile His Ala His Phe Thr Gly Leu Arg 210 215 220 Tyr Leu Leu Tyr Asn Phe Pro Met Thr Cys Ala Phe Ile Gly Val Ala 225 230 235 240 Ser Asn Phe Thr Phe Leu Ser Val Ile Val Leu Phe Ser Tyr Met Gln 245 250 255 Trp Val Trp Gly Gly Ile Trp Pro Arg His Arg Phe Ser Leu Gln Val 260 265 270 Asn Ile Arg Lys Arg Asp Asn Ser Arg Lys Glu Val Gln Arg Arg Ile 275 280 285 Ser Ala His Gln Pro Gly Pro Glu Gly Gln Glu Glu Ser Thr Pro Gln 290 295 300 Ser Asp Val Thr Glu Asp Gly Glu Ser Pro Glu Asp Pro Ser Gly Thr 305 310 315 320 Glu Val Ser Cys Pro Arg Arg Arg Asn Gln Ile Ser Ser Pro 325 330 (2) INFORMATION FOR SEQ ID NO: 35: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 276 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 35: Met Thr His Pro Gly Thr Gly Asp Ile Ile Ala Val Met Ile Thr Glu 1 5 10 15 Leu Arg Gly Lys Asp Ile Leu Ser Tyr Leu Glu Lys Asn Ile Ser Val 20 25 30 Gln Met Thr Ile Ala Val Gly Thr Arg Met Pro Pro Lys Asn Phe Ser 35 40 45 Arg Gly Ser Leu Val Phe Val Ser Ile Ser Phe Ile Val Leu Met Ile 50 55 60 Ile Ser Ser Ala Trp Leu Ile Phe Tyr Phe Ile Gln Lys Ile Arg Tyr 65 70 75 80 Thr Asn Ala Arg Asp Arg Asn Gln Arg Arg Leu Gly Asp Ala Ala Lys 85 90 95 Lys Ala Ile Ser Lys Leu Thr Thr Arg Thr Val Lys Lys Gly Asp Lys 100 105 110 Glu Thr Asp Pro Asp Phe Asp His Cys Ala Val Cys Ile Glu Ser Tyr 115 120 125 Lys Gln Asn Asp Val Val Arg Ile Leu Pro Cys Lys His Val Phe His 130 135 140 Lys Ser Cys Val Asp Pro Trp Leu Ser Glu His Cys Thr Cys Pro Met 145 150 155 160 Cys Lys Leu Asn Ile Leu Lys Ala Leu Gly Ile Val Pro Asn Leu Pro 165 170 175 Cys Thr Asp Asn Val Ala Phe Asp Met Glu Arg Leu Thr Arg Thr Gln 180 185 190 Ala Val Asn Arg Arg Ser Ala Leu Gly Asp Leu Ala Gly Asp Asn Ser 195 200 205 Leu Gly Leu Glu Pro Leu Arg Thr Ser Gly Ile Ser Pro Leu Pro Gln 210 215 220 Asp Gly Glu Leu Thr Pro Arg Thr Gly Glu Ile Asn Ile Ala Val Thr 225 230 235 240 Lys Glu Trp Phe Ile Ile Ala Ser Phe Gly Leu Leu Ser Ala Leu Thr 245 250 255 Leu Cys Tyr Met Ile Ile Arg Ala Thr Ala Ser Leu Asn Ala Asn Glu 260 265 270 Val Glu Trp Phe 275 (2) INFORMATION FOR SEQ ID NO: 36: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 210 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 36: Met Ala Asn Ser Gly Leu Gln Leu Leu Gly Phe Ser Met Ala Leu Leu 1 5 10 15 Gly Trp Val Gly Leu Val Ala Cys Thr Ala Ile Pro Gln Trp Gln Met 20 25 30 Ser Ser Tyr Ala Gly Asp Asn Ile Ile Thr Ala Gln Ala Met Tyr Lys 35 40 45 Gly Leu Trp Met Asp Cys Val Thr Gln Ser Thr Gly Met Met Ser Cys 50 55 60 Lys Met Tyr Asp Ser Val Leu Ala Leu Ser Ala Ala Leu Gln Ala Thr 65 70 75 80 Arg Ala Leu Met Val Val Ser Leu Val Leu Gly Phe Leu Ala Met Phe 85 90 95 Val Ala Thr Met Gly Met Lys Cys Thr Arg Cys Gly Gly Asp Asp Lys 100 105 110 Val Lys Lys Ala Arg Ile Ala Met Gly Gly Gly Ile Ile Phe Ile Val 115 120 125 Ala Gly Leu Ala Ala Leu Val Ala Cys Ser Trp Tyr Gly His Gln Ile 130 135 140 Val Thr Asp Phe Tyr Asn Pro Leu Ile Pro Thr Asn Ile Lys Tyr Glu 145 150 155 160 Phe Gly Pro Ala Ile Phe Ile Gly Trp Ala Gly Ser Ala Leu Val Ile 165 170 175 Leu Gly Gly Ala Leu Leu Ser Cys Ser Cys Pro Gly Asn Glu Ser Lys 180 185 190 Ala Gly Tyr Arg Ala Pro Arg Ser Tyr Pro Lys Ser Asn Ser Ser Lys 195 200 205 Glu Tyr 210 (2) INFORMATION FOR SEQ ID NO: 37: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 476 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 37: Met Ile Arg Pro Gln Leu Arg Thr Ala Gly Leu Gly Arg Cys Leu Leu 1 5 10 15 Pro Gly Leu Leu Leu Leu Leu Val Pro Val Leu Trp Ala Gly Ala Glu 20 25 30 Lys Leu His Thr Gln Pro Ser Cys Pro Ala Val Cys Gln Pro Thr Arg 35 40 45 Cys Pro Ala Leu Pro Thr Cys Ala Leu Gly Thr Thr Pro Val Phe Asp 50 55 60 Leu Cys Arg Cys Cys Arg Val Cys Pro Ala Ala Glu Arg Glu Val Cys 65 70 75 80 Gly Gly Ala Gln Gly Gln Pro Cys Ala Pro Gly Leu Gln Cys Leu Gln 85 90 95 Pro Leu Arg Pro Gly Phe Pro Ser Thr Cys Gly Cys Pro Thr Leu Gly 100 105 110 Gly Ala Val Cys Gly Ser Asp Arg Arg Thr Tyr Pro Ser Met Cys Ala 115 120 125 Leu Arg Ala Glu Asn Arg Ala Ala Arg Arg Leu Gly Lys Val Pro Ala 130 135 140 Val Pro Val Gln Trp Gly Asn Cys Gly Asp Thr Gly Thr Arg Ser Ala 145 150 155 160 Gly Pro Leu Arg Arg Asn Tyr Asn Phe Ile Ala Ala Val Val Glu Lys 165 170 175 Val Ala Pro Ser Val Val His Val Gln Leu Trp Gly Arg Leu Leu His 180 185 190 Gly Ser Arg Leu Val Pro Val Tyr Ser Gly Ser Gly Phe Ile Val Ser 195 200 205 Glu Asp Gly Leu Ile Ile Thr Asn Ala His Val Val Arg Asn Gln Gln 210 215 220 Trp Ile Glu Val Val Leu Gln Asn Gly Ala Arg Tyr Glu Ala Val Val 225 230 235 240 Lys Asp Ile Asp Leu Lys Leu Asp Leu Ala Val Ile Lys Ile Glu Ser 245 250 255 Asn Ala Glu Leu Pro Val Leu Met Leu Gly Arg Ser Ser Asp Leu Arg 260 265 270 Ala Gly Glu Phe Val Val Ala Leu Gly Ser Pro Phe Ser Leu Gln Asn 275 280 285 Thr Ala Thr Ala Gly Ile Val Ser Thr Lys Gln Arg Gly Gly Lys Glu 290 295 300 Leu Gly Met Lys Asp Ser Asp Met Asp Tyr Val Gln Ile Asp Ala Thr 305 310 315 320 Ile Asn Tyr Gly Asn Ser Gly Gly Pro Leu Val Asn Leu Asp Gly Asp 325 330 335 Val Ile Gly Val Asn Ser Leu Arg Val Thr Asp Gly Ile Ser Phe Ala 340 345 350 Ile Pro Ser Asp Arg Val Arg Gln Phe Leu Ala Glu Tyr His Glu His 355 360 365 Gln Met Lys Gly Lys Ala Phe Ser Asn Lys Lys Tyr Leu Gly Leu Gln 370 375 380 Met Leu Ser Leu Thr Val Pro Leu Ser Glu Glu Leu Lys Met His Tyr 385 390 395 400 Pro Asp Phe Pro Asp Val Ser Ser Gly Val Tyr Val Cys Lys Val Val 405 410 415 Glu Gly Thr Ala Ala Gln Ser Ser Gly Leu Arg Asp His Asp Val Ile 420 425 430 Val Asn Ile Asn Gly Lys Pro Ile Thr Thr Thr Thr Asp Val Val Lys 435 440 445 Ala Leu Asp Ser Asp Ser Leu Ser Met Ala Val Leu Arg Gly Lys Asp 450 455 460 Asn Leu Leu Leu Thr Val Ile Pro Glu Thr Ile Asn 465 470 475 (2) INFORMATION FOR SEQ ID NO: 38: (i) SEQUENCE CHARACTERISTICS: (A) LENGTH: 266 amino acids (B) TYPE: amino acid (C) STRANDEDNESS: single (D) TOPOLOGY: linear (ii) MOLECULE TYPE: None (xi) SEQUENCE DESCRIPTION: SEQ ID NO: 38: Met Val Lys Val Thr Phe Asn Ser Ala Leu Ala Gln Lys Glu Ala Lys 1 5 10 15 Lys Asp Glu Pro Glu Ser Gly Glu Glu Ala Leu Ile Ile Pro Pro Asp 20 25 30 Ala Val Ala Val Asp Cys Lys Asp Pro Asp Asp Val Val Pro Val Gly 35 40 45 Gln Arg Arg Ala Trp Cys Trp Cys Met Cys Phe Gly Leu Ala Phe Met 50 55 60 Leu Ala Gly Val Ile Leu Gly Gly Ala Tyr Leu Tyr Lys Tyr Phe Ala 65 70 75 80 Leu Gln Pro Asp Asp Val Tyr Tyr Cys Gly Ile Lys Tyr Ile Lys Asp 85 90 95 Asp Val Ile Leu Asn Glu Pro Ser Ala Asp Ala Pro Ala Ala Leu Tyr 100 105 110 Gln Thr Ile Glu Glu Asn Ile Lys Ile Phe Glu Glu Glu Glu Val Glu 115 120 125 Phe Ile Ser Val Pro Val Pro Glu Phe Ala Asp Ser Asp Pro Ala Asn 130 135 140 Ile Val His Asp Phe Asn Lys Lys Leu Thr Ala Tyr Leu Asp Leu Asn 145 150 155 160 Leu Asp Lys Cys Tyr Val Ile Pro Leu Asn Thr Ser Ile Val Met Pro 165 170 175 Pro Arg Asn Leu Leu Glu Leu Leu Ile Asn Ile Lys Ala Gly Thr Tyr 180 185 190 Leu Pro Gln Ser Tyr Leu Ile His Glu His Met Val Ile Thr Asp Arg 195 200 205 Ile Glu Asn Ile Asp His Leu Gly Phe Phe Ile Tyr Arg Leu Cys His 210 215 220 Asp Lys Glu Thr Tyr Lys Leu Gln Arg Arg Glu Thr Ile Lys Gly Ile 225 230 235 240 Gln Lys Arg Glu Ala Ser Asn Cys Phe Ala Ile Arg His Phe Glu Asn 245 250 255 Lys Phe Ala Val Glu Thr Leu Ile Cys Ser 260 265 

We claim:
 1. An isolated and purified human protein having an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and
 38. 2. An isolated and purified human protein having an amino acid sequence which is at least 85% identical to an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and
 38. 3. An isolated and purified human polypeptide comprising at least 6 contiguous amino acids of an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and
 38. 4. A fusion protein comprising a first protein segment and a second protein segment fused together by means of a peptide bond, wherein the first protein segment consists of at least 6 contiguous amino acids selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and
 38. 5. A preparation of antibodies which specifically bind to the human protein of claim
 1. 6. An isolated and purified subgenomic polynucleotide having a nucleotide sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and
 19. 7. An isolated gene corresponding to a cDNA sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and
 19. 8. A DNA construct for expressing all or a portion of a human protein having an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID Nos: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38, comprising: a promoter; and a polynucleotide segment encoding at least 6 contiguous amino acids of the human protein, wherein the polynucleotide segment is located downstream from the promoter, wherein transcription of the polynucleotide segment initiates at or 3′ to the promoter.
 9. A host cell comprising a DNA construct comprising: a promoter; and a polynucleotide segment encoding at least 6 contiguous amino acids of a human protein having an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID NOs: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38, wherein the polynucleotide segment is located downstream from the promoter and wherein transcription of the polynucleotide segment initiates at or 3′ to the promoter.
 10. A homologously recombinant cell having incorporated therein a new transcription initiation unit, wherein the new transcription initiation unit comprises in 5′ to 3′ order: (a) an exogenous regulatory sequence; (b) an exogenous exon; and (c) a splice donor site, wherein the transcription initiation unit is located upstream to a coding sequence of a gene, wherein the gene comprises a nucleotide sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 and wherein the exogenous regulatory sequence controls transcription of the coding sequence of the gene.
 11. A method of producing a human protein, comprising the steps of: growing a culture of a cell comprising a DNA construct comprising (1) a promoter and (2) a polynucleotide segment encoding at least 6 contiguous amino acids of a human protein having an amino acid sequence selected from the group consisting of the amino acid sequences shown in SEQ ID NOs: 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, and 38, wherein the polynucleotide segment is located downstream from the promoter and wherein transcription of the polynucleotide segment initiates at or 3′ to the promoter; and purifying the protein from the culture.
 12. A method of producing a human protein, comprising the steps of: growing a culture of a homologously recombinant cell having incorporated therein a new transcription initiation unit, wherein the new transcription initiation unit comprises in 5′ to 3′ order: (a) an exogenous regulatory sequence; (b) an exogenous exon; and (c) a splice donor site, wherein the transcription initiation unit is located upstream to a coding sequence of a gene, wherein the gene comprises a nucleotide sequence selected from the group consisting of the nucleotide sequences shown in SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 and wherein the exogenous regulatory sequence controls transcription of the coding sequence of the gene; and purifying the protein from the culture.
 13. A method of identifying a secreted polypeptide which is modified by rough microsomes, comprising the steps of: transcribing in vitro a population of cDNA molecules whereby a population of cRNA molecules is formed; translating a first portion of the population of cRNA molecules in vitro in the absence of rough microsomes whereby a first population of polypeptides is formed; translating a second portion of the population of cRNA molecules in vitro in the presence of rough microsomes whereby a second population of polypeptides is formed; comparing the first population of polypeptides with the second population of polypeptides; and detecting polypeptide members of the second population which have been modified by the rough microsomes. 